Activity
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3000 actions
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| Cerebral vascular malformations v1.65 | SLC2A10 | Louise Daugherty Source NHS GMS was added to SLC2A10. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | SAMHD1 | Louise Daugherty Source NHS GMS was added to SAMHD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | RASA1 | Louise Daugherty Source NHS GMS was added to RASA1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | PKD2 | Louise Daugherty Source NHS GMS was added to PKD2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | PKD1 | Louise Daugherty Source NHS GMS was added to PKD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | PDCD10 | Louise Daugherty Source NHS GMS was added to PDCD10. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | PCNT | Louise Daugherty Source NHS GMS was added to PCNT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | NOTCH3 | Louise Daugherty Source NHS GMS was added to NOTCH3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | NF1 | Louise Daugherty Source NHS GMS was added to NF1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | MYH11 | Louise Daugherty Source NHS GMS was added to MYH11. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | KRIT1 | Louise Daugherty Source NHS GMS was added to KRIT1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | JAG1 | Louise Daugherty Source NHS GMS was added to JAG1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | HBB | Louise Daugherty Source NHS GMS was added to HBB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | GUCY1A3 | Louise Daugherty Source NHS GMS was added to GUCY1A3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | FLVCR2 | Louise Daugherty Source NHS GMS was added to FLVCR2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | ENG | Louise Daugherty Source NHS GMS was added to ENG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | ELN | Louise Daugherty Source NHS GMS was added to ELN. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | COL3A1 | Louise Daugherty Source NHS GMS was added to COL3A1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | CEP152 | Louise Daugherty Source NHS GMS was added to CEP152. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | CCM2 | Louise Daugherty Source NHS GMS was added to CCM2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | CBL | Louise Daugherty Source NHS GMS was added to CBL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | ATR | Louise Daugherty Source NHS GMS was added to ATR. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | ADA2 | Louise Daugherty Source NHS GMS was added to ADA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | ACVRL1 | Louise Daugherty Source NHS GMS was added to ACVRL1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.65 | ACTA2 | Louise Daugherty Source NHS GMS was added to ACTA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.64 | MYH11 | Louise Daugherty Classified gene: MYH11 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.64 | MYH11 | Louise Daugherty Gene: myh11 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.63 | MYH11 | Louise Daugherty changed review comment from: Comment on list classification: Changed rating from Red to Green - this gene was deemed relevant to the GMS panel R336 Cerebral vascular malformations; to: Comment on list classification: Changed rating to Amber - this gene was deemed relevant to the GMS panel R336 Cerebral vascular malformations. This was a new gene recommended to be rated as Green but after further clinical expert it was decided to rate as Amber until there was sufficient evidence | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.63 | MYH11 | Louise Daugherty changed review comment from: New gene rated Green - deemed relevant to the GMS panel R336 Cerebral vascular malformations; to: New gene rated Amber - deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.63 | MYH11 | Louise Daugherty edited their review of gene: MYH11: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.63 | MYH11 | Louise Daugherty Classified gene: MYH11 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.63 | MYH11 | Louise Daugherty Gene: myh11 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.62 | SMAD9 | Louise Daugherty Classified gene: SMAD9 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.62 | SMAD9 | Louise Daugherty Gene: smad9 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.61 | SMAD9 | Louise Daugherty commented on gene: SMAD9: New gene rated Amber- deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.61 | SMAD9 |
Louise Daugherty gene: SMAD9 was added gene: SMAD9 was added to Cerebral vascular malformations. Sources: Expert list Mode of inheritance for gene: SMAD9 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Review for gene: SMAD9 was set to AMBER Added comment: Review from clinical expert (Vijeya Ganesan: GOSH / ICH): consider for this panel. GEL clinical team (Helen Brittain) Review of PMID 29844917 suggests one case with cerebral AVMs and a supportive animal model - currently rated amber pending further evidence Sources: Expert list |
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| Cerebral vascular malformations v1.60 | EPHB4 | Louise Daugherty Classified gene: EPHB4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.60 | EPHB4 | Louise Daugherty Added comment: Comment on list classification: New Amber gene - this gene was deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.60 | EPHB4 | Louise Daugherty Gene: ephb4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.59 | EPHB4 | Louise Daugherty commented on gene: EPHB4: New gene rated Amber - deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.59 | EPHB4 |
Louise Daugherty gene: EPHB4 was added gene: EPHB4 was added to Cerebral vascular malformations. Sources: Expert list Mode of inheritance for gene: EPHB4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: EPHB4 were set to Capillary malformation-arteriovenous malformation 2, 618196 Review for gene: EPHB4 was set to AMBER Added comment: Review from clinical expert (Vijeya Ganesan: GOSH / ICH): consider for this panel. GEL clinical team (Helen Brittain) Review of PMID 28687708 suggests that 3/110 patients had CNS lesions - therefore rated as amber pending further evidence Sources: Expert list |
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| Cerebral vascular malformations v1.58 | MRVI1 | Louise Daugherty commented on gene: MRVI1: New gene rated Amber - deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.58 | YY1AP1 | Louise Daugherty commented on gene: YY1AP1: New gene rated Green - deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.58 | CBL | Louise Daugherty commented on gene: CBL: New gene rated Green - deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.58 | MYH11 | Louise Daugherty commented on gene: MYH11: New gene rated Green - deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.58 | CTSA | Louise Daugherty commented on gene: CTSA: New gene rated Red - deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.58 | MRVI1 | Louise Daugherty Classified gene: MRVI1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.58 | MRVI1 | Louise Daugherty Added comment: Comment on list classification: New gene rated Amber- this gene was deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.58 | MRVI1 | Louise Daugherty Gene: mrvi1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.57 | MRVI1 |
Louise Daugherty gene: MRVI1 was added gene: MRVI1 was added to Cerebral vascular malformations. Sources: Expert list Mode of inheritance for gene: MRVI1 was set to Unknown Review for gene: MRVI1 was set to AMBER Added comment: Review from clinical expert (Vijeya Ganesan: GOSH / ICH): evidence emerging of potential risk factor for Moya-Moya within NF1 patients. Sources: Expert list |
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| Cerebral vascular malformations v1.56 | YY1AP1 | Louise Daugherty Classified gene: YY1AP1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.56 | YY1AP1 | Louise Daugherty Added comment: Comment on list classification: Changed rating from Red to Green - this gene was deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.56 | YY1AP1 | Louise Daugherty Gene: yy1ap1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.55 | YY1AP1 |
Louise Daugherty gene: YY1AP1 was added gene: YY1AP1 was added to Cerebral vascular malformations. Sources: Expert list Mode of inheritance for gene: YY1AP1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: YY1AP1 were set to Grange syndrome, 602531 Review for gene: YY1AP1 was set to GREEN Added comment: Review from clinical expert (Vijeya Ganesan: GOSH / ICH): considered relevant for this panel. Sources: Expert list |
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| Cerebral vascular malformations v1.54 | CBL | Louise Daugherty Classified gene: CBL as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.54 | CBL | Louise Daugherty Added comment: Comment on list classification: Changed rating from Red to Green - this gene was deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.54 | CBL | Louise Daugherty Gene: cbl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.53 | CBL | Louise Daugherty reviewed gene: CBL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.53 | CBL | Louise Daugherty Phenotypes for gene: CBL were changed from early-onset moyamoya angiopathy to early-onset moyamoya angiopathy; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, 613563 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.52 | MYH11 | Louise Daugherty Classified gene: MYH11 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.52 | MYH11 | Louise Daugherty Added comment: Comment on list classification: Changed rating from Red to Green - this gene was deemed relevant to the GMS panel R336 Cerebral vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.52 | MYH11 | Louise Daugherty Gene: myh11 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.51 | MYH11 | Louise Daugherty edited their review of gene: MYH11: Added comment: Review from clinical expert (Vijeya Ganesan: GOSH / ICH): multi-system vascular disease, green rating.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.51 | MYH11 | Louise Daugherty Phenotypes for gene: MYH11 were changed from moyamoya-like angiopathy to moyamoya-like angiopath; Aortic aneurysm, familial thoracic 4, 132900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.50 | MYH11 | Louise Daugherty Classified gene: MYH11 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.50 | MYH11 | Louise Daugherty Added comment: Comment on list classification: added gene back to panel due to recent update as part of the GMS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.50 | MYH11 | Louise Daugherty Gene: myh11 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral vascular malformations v1.49 | CTSA |
Louise Daugherty gene: CTSA was added gene: CTSA was added to Cerebral vascular malformations. Sources: Expert list Mode of inheritance for gene: CTSA was set to Unknown Review for gene: CTSA was set to RED Added comment: Combined reviews: Ian Berry (YNELGH) & GEL clinical team (Richard Scott & Helen Brittain) - red in view of lack of a relevant phenotype for this panel Sources: Expert list |
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| Renal ciliopathies v1.0 | PDE6D | Ellen McDonagh reviewed gene: PDE6D: Rating: AMBER; Mode of pathogenicity: None; Publications: 30423442; Phenotypes: Joubert syndrome type 22 (JBTS22); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Neurological ciliopathies v0.7 | PDE6D | Ellen McDonagh reviewed gene: PDE6D: Rating: AMBER; Mode of pathogenicity: None; Publications: 30423442; Phenotypes: Joubert syndrome type 22 (JBTS22); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ophthalmological ciliopathies v0.11 | PDE6D | Ellen McDonagh reviewed gene: PDE6D: Rating: AMBER; Mode of pathogenicity: None; Publications: 30423442; Phenotypes: Joubert syndrome type 22 (JBTS22); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare multisystem ciliopathy disorders v1.121 | PDE6D | Ellen McDonagh reviewed gene: PDE6D: Rating: AMBER; Mode of pathogenicity: None; Publications: 30423442; Phenotypes: Joubert syndrome type 22 (JBTS22); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.141 | PDE6D | Ellen McDonagh reviewed gene: PDE6D: Rating: AMBER; Mode of pathogenicity: None; Publications: 30423442; Phenotypes: Joubert syndrome type 22 (JBTS22); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1134 | PDE6D | Ellen McDonagh Classified gene: PDE6D as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1134 | PDE6D | Ellen McDonagh Added comment: Comment on list classification: Gene added by external reviewer, and promoted to Amber due to one family and a recent additional case. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1134 | PDE6D | Ellen McDonagh Gene: pde6d has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.497 | PCYT2 | Ellen McDonagh reviewed gene: PCYT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1133 | PCYT2 | Ellen McDonagh Classified gene: PCYT2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1133 | PCYT2 | Ellen McDonagh Added comment: Comment on list classification: This gene was added by an external reviewer and rated Green. This is currently Green on the Hereditary spastic paraplegia gene panel (Version 1.210), and confirmed with Zerin Hyder (Genomics England Clinical Team) that this is appropriate to be Green on the ID panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1133 | PCYT2 | Ellen McDonagh Gene: pcyt2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.108 | BICD2 | Rebecca Foulger Phenotypes for gene: BICD2 were changed from Spinal muscular atrophy, lower extremity-predominant, 2A, 615290; autosomal dominant, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 to arthrogryposis multiplex congenita; Spinal muscular atrophy, lower extremity-predominant, 2A, 615290; autosomal dominant, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.107 | BICD2 | Rebecca Foulger Classified gene: BICD2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.107 | BICD2 | Rebecca Foulger Added comment: Comment on list classification: Promoted BICD2 from Red to Green based on recent literature evidence and Green review by Zerin Hyder (Genomics England Clinical Team). Sufficient unrelated cases of AMC for inclusion on panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.107 | BICD2 | Rebecca Foulger Gene: bicd2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.106 | BICD2 | Rebecca Foulger Publications for gene: BICD2 were set to 28635954 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.105 | BICD2 | Rebecca Foulger Mode of inheritance for gene: BICD2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.104 | BICD2 |
Zerin Hyder changed review comment from: PMID:27751653 (Ravenscroft et al., 2016) report two unrelated probands (a German male and a boy from a Welsh mother and NZ/European father) that presented in utero with reduced fetal movement. Both cases had arthrogryposis multiplex congenita (AMC) and hypotonia diagnosed at birth . The same missense de novo variant in BICD2 (p.Arg694Cys) was present in both probands. PMID:29274205 (Ahmed et al., 2018) report a stillborn female fetus (case 4) with pterygia and arthrogryposis with a heterozygous likely-pathogenic variant in BICD2. Phenotypes included an abnormal fetal position with fixed limbs, hydrops fetalis and polyhydramnios. A heterozygous p.Asn700Lys variant in BICD2 was revealed. However, compound het variants of unknown significance in AGRN were also identified, so the authors can not be certain that BICD2 is the causative variant. PMID:28635954 (Storbeck et al., 2017) describe 3 individuals of independent families with severe severe arthrogryposis multiplex congenita (AMC), respiratory insufficiency, and early lethality caused by three BICD2 variants (p.Arg694Cys, p.Gln194Arg and p.Cys542Trp, 2 of which are proven to be de novo). They also describe an asymptomatic women with subclinical findings with the previously described p.(Thr703Met) variant. PMID: 30054298. In 2 unrelated patients with muscular atrophy and arthrogryposis Koboldt et al. (2018) identified a de novo heterozygous c.1636_1638delAAT variant in the BICD2 gene. The mutation, which was found by whole-exome or whole-genome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but protein modeling indicated that the variant is within a region that interacts with the molecular kinesin motor and that the mutation would alter protein structure.; to: PMID:27751653 (Ravenscroft et al., 2016) report two unrelated probands (a German male and a boy from a Welsh mother and NZ/European father) that presented in utero with reduced fetal movement. Both cases had arthrogryposis multiplex congenita (AMC) and hypotonia diagnosed at birth . The same missense de novo variant in BICD2 (p.Arg694Cys) was present in both probands. PMID:29274205 (Ahmed et al., 2018) report a stillborn female fetus (case 4) with pterygia and arthrogryposis with a heterozygous likely-pathogenic variant in BICD2. Phenotypes included an abnormal fetal position with fixed limbs, hydrops fetalis and polyhydramnios. A heterozygous p.Asn700Lys variant in BICD2 was revealed. However, compound het variants of unknown significance in AGRN were also identified, so the authors can not be certain that BICD2 is the causative variant. PMID:28635954 (Storbeck et al., 2017) describe 3 individuals of independent families with severe arthrogryposis multiplex congenita (AMC), respiratory insufficiency, and early lethality caused by three BICD2 variants (p.Arg694Cys, p.Gln194Arg and p.Cys542Trp, 2 of which are proven to be de novo). They also describe an asymptomatic woman with subclinical findings with the previously described p.(Thr703Met) variant. PMID: 30054298. In 2 unrelated patients with muscular atrophy and arthrogryposis Koboldt et al. (2018) identified a de novo heterozygous c.1636_1638delAAT variant in the BICD2 gene. The mutation, which was found by whole-exome or whole-genome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but protein modeling indicated that the variant is within a region that interacts with the molecular kinesin motor and that the mutation would alter protein structure. |
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| Arthrogryposis v2.104 | BICD2 | Zerin Hyder reviewed gene: BICD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27751653, 29274205, 28635954, 30054298; Phenotypes: Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant 615290, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.370 | BICD2 | Rebecca Foulger Publications for gene: BICD2 were set to 27751653; 29274205; 28635954 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.369 | BICD2 | Rebecca Foulger Phenotypes for gene: BICD2 were changed from PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; arthrogryposis multiplex congenita (AMC); reduced fetal movements; hydrops fetalis to PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; arthrogryposis multiplex congenita (AMC); reduced fetal movements; hydrops fetalis; Pterygium | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.368 | BICD2 | Rebecca Foulger Phenotypes for gene: BICD2 were changed from PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 to PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291; arthrogryposis multiplex congenita (AMC); reduced fetal movements; hydrops fetalis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.367 | BICD2 | Rebecca Foulger commented on gene: BICD2: PMID:28635954 (Storbeck et al., 2017) describe 3 individuals of independent families with severe severe arthrogryposis multiplex congenita (AMC), respiratory insufficiency, and early lethality caused by three BICD2 variants (p.Arg694Cys, p.Gln194Arg and p.Cys542Trp, 2 of which are proven to be de novo). They also describe an asymptomatic women with subclinical findings with the previously described p.(Thr703Met) variant. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.367 | BICD2 | Rebecca Foulger commented on gene: BICD2: PMID:29274205 (Ahmed et al., 2018) report a stillborn female fetus (case 4) with pterygia and arthrogryposis with a heterozygous likely-pathogenic variant in BICD2. Phenotypes included an abnormal fetal position with fixed limbs, hydrops fetalis and polyhydramnios. A heterozygous p.Asn700Lys variant in BICD2 was revealed. However, compound het variants of unknown significance in AGRN were also identified, so the authors can not be certain that BICD2 is the causative variant. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.367 | BICD2 | Rebecca Foulger commented on gene: BICD2: PMID:27751653 (Ravenscroft et al., 2016) report two unrelated probands (a German male and a boy from a Welsh mother and NZ/European father) that presented in utero with reduced fetal movement. Both cases had arthrogryposis multiplex congenita (AMC) and hypotonia diagnosed at birth. The same missense de novo variant in BICD2 (p.Arg694Cys) was present in both probands. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.104 | BICD2 | Rebecca Foulger Phenotypes for gene: BICD2 were changed from Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 to Spinal muscular atrophy, lower extremity-predominant, 2A, 615290; autosomal dominant, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.103 | BICD2 | Rebecca Foulger Phenotypes for gene: BICD2 were changed from to Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.102 | BICD2 | Rebecca Foulger Publications for gene: BICD2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.367 | BICD2 | Rebecca Foulger commented on gene: BICD2: OMIM Clinical Synopsis for MIM:618291 now mentions onset in Utero, including fractures in utero and decreased fetal movements, as noted by Rhiannon Mellis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.141 | EPHA4 | Eleanor Williams changed review comment from: Comment on list classification: Rating this gene as amber for now. Deletion of a region including this gene has been reported in PMID: 25959774 - Lupiáñez et al 2015, however the mechanism for pathogenicity needs clarification.; to: Comment on list classification: Rating this gene as amber for now. Deletion of a region including this gene has been reported in PMID: 25959774 - Lupiáñez et al 2015, however the mechanism for pathogenicity and deliniating reigion needs clarification. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.367 | BICD2 | Rebecca Foulger Mode of pathogenicity for gene: BICD2 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.366 | BICD2 | Rebecca Foulger Phenotypes for gene: BICD2 were changed from PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE to PROXIMAL SPINAL MUSCULAR ATROPHY WITH AUTOSOMAL-DOMINANT INHERITANCE; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.365 | BICD2 | Rebecca Foulger Publications for gene: BICD2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.101 | TTN | Rebecca Foulger changed review comment from: Comment on mode of inheritance: Changed MOI from 'BOTH monoallelic and biallelic' to 'BIALLELIC' to match MOI on 'Neuromuscular arthrogryposis' panel V0.21 and review on DDG2P panel by Lucy Raymond.; to: Comment on mode of inheritance: With agreement from Zerin Hyder, changed MOI from 'BOTH monoallelic and biallelic' to 'BIALLELIC' to match MOI on 'Neuromuscular arthrogryposis' panel V0.21 and review on DDG2P panel by Lucy Raymond. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.140 | WDPCP | Eleanor Williams Publications for gene: WDPCP were set to 25427950 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.139 | WDPCP | Eleanor Williams Classified gene: WDPCP as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.139 | WDPCP | Eleanor Williams Added comment: Comment on list classification: Promoting this gene to green. It has limited evidence in association with Bardet-Biedl syndrome 15, but there are 3 cases reported in association with Oral facial digital syndrome and plausible disease causing variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.139 | WDPCP | Eleanor Williams Gene: wdpcp has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.138 | EPHA4 | Eleanor Williams Classified gene: EPHA4 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.138 | EPHA4 | Eleanor Williams Added comment: Comment on list classification: Rating this gene as amber for now. Deletion of a region including this gene has been reported in PMID: 25959774 - Lupiáñez et al 2015, however the mechanism for pathogenicity needs clarification. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.138 | EPHA4 | Eleanor Williams Gene: epha4 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.137 | EPHA4 | Eleanor Williams commented on gene: EPHA4: A curation request has been submitted to Clingen regarding the regions of deletion, duplication and inversion around EPHA4 reported in PMID: 25959774 - Lupiáñez et al 2015. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.137 | EPHA4 |
Eleanor Williams changed review comment from: EPHA4 not associated with any phenotype in OMIM or Gene2Phenotype. PMID: 25959774 - Lupiáñez et al 2015 - studied limb abnormalities in 3 sets of families: Group 1 - 3 unrelated families with a dominantly inherited novel type of brachydactyly, characterized by short digits predominantly on the preaxial (radial) side resulting in stub thumbs, short index fingers and a cutaneous web between the first and second fingers. aCGH revealed heterozygous deletions of 1.75–1.9 Mb on chromosome 2q35–36 in all three affected families. All three deletions include the EPHA4 gene along with a large portion of its surrounding TAD and extend into the non-coding part of the adjacent PAX3 TAD (topologically associated domain), thereby removing the predicted boundary between the EPHA4 and PAX3 TADs. Mutant mice with a deletion corresponding to the human disease alleles recapitulated the phenotype observed in patients. Group 2 - 2 unrelated families with F-syndrome, a limb malformation syndrome characterized by severe and complex syndactyly, often involving the first and second fingers, and polydactyly of the feet. By whole genome sequencing they detected a ~1.1 Mb heterozygous inversion in family F1 and a ~1.4 Mb heterozygous duplication, arranged in direct tandem orientation, in family F2. The telomeric breakpoints were located 1.4 Mb away from the EPHA4 gene within the gene desert in the case of the inversion, and 1.2 Mb in the case of the duplication. Heterozygous as well as homozygous newborn mice generated via tetraploid aggregation died shortly after birth of unknown cause and did not show overt limb phenotypes or other morphological defects Group 3 - a family that carries a heterozygous ~900 kb duplication in chromosomal region 2q35 that results in severe polysyndactyly and craniofacial abnormalities. The phenotype is reminiscent of the doublefoot (Dbf) mouse mutant, which also features massive polysyndactyly and was shown to be caused by a ~600 kb deletion affecting the same region (Babbs et al., 2008) Using 4C-seq they show that In wild-type distal limbs, there was minimal interaction of Pax3, Wnt6 and Ihh with non-coding sequences in the Epha4 TAD. In contrast, all three genes showed substantial interaction with the Epha4 TAD in the mutants. Similar results were found using patient fibroblasts. Genomic re-arrangements in the Epha4 TAD can result in limb abnormalities. It maybe best to represent these as regions of gain or loss in PanelApp; to: EPHA4 not associated with any phenotype in OMIM or Gene2Phenotype. PMID: 25959774 - Lupiáñez et al 2015 - studied limb abnormalities in 3 sets of families: Group 1 - 3 unrelated families with a dominantly inherited novel type of brachydactyly, characterized by short digits predominantly on the preaxial (radial) side resulting in stub thumbs, short index fingers and a cutaneous web between the first and second fingers. aCGH revealed heterozygous deletions of 1.75–1.9 Mb on chromosome 2q35–36 in all three affected families. All three deletions include the EPHA4 gene along with a large portion of its surrounding TAD and extend into the non-coding part of the adjacent PAX3 TAD (topologically associated domain), thereby removing the predicted boundary between the EPHA4 and PAX3 TADs. Mutant mice with a deletion corresponding to the human disease alleles recapitulated the phenotype observed in patients. They detected a significant upregulation of Pax3 in DelB/+ limbs in mice, and DelB/+ (brachydactyly-like deletion) mice showed strong misexpression of Pax3 in the distal anterior part of the autopod, in a pattern resembling endogenous Epha4 expression. Group 2 - 2 unrelated families with F-syndrome, a limb malformation syndrome characterized by severe and complex syndactyly, often involving the first and second fingers, and polydactyly of the feet. By whole genome sequencing they detected a ~1.1 Mb heterozygous inversion in family F1 and a ~1.4 Mb heterozygous duplication, arranged in direct tandem orientation, in family F2. The telomeric breakpoints were located 1.4 Mb away from the EPHA4 gene within the gene desert in the case of the inversion, and 1.2 Mb in the case of the duplication. Heterozygous as well as homozygous newborn mice generated via tetraploid aggregation died shortly after birth of unknown cause and did not show overt limb phenotypes or other morphological defects Group 3 - a family that carries a heterozygous ~900 kb duplication in chromosomal region 2q35 that results in severe polysyndactyly and craniofacial abnormalities. The phenotype is reminiscent of the doublefoot (Dbf) mouse mutant, which also features massive polysyndactyly and was shown to be caused by a ~600 kb deletion affecting the same region (Babbs et al., 2008) Using 4C-seq they show that In wild-type distal limbs, there was minimal interaction of Pax3, Wnt6 and Ihh with non-coding sequences in the Epha4 TAD. In contrast, all three genes showed substantial interaction with the Epha4 TAD in the mutants. Similar results were found using patient fibroblasts. Genomic re-arrangements in the Epha4 TAD can result in limb abnormalities. It maybe best to represent these as regions of gain or loss in PanelApp |
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| Adult onset dystonia, chorea or related movement disorder v1.0 | Louise Daugherty promoted panel to version 1.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.131 | Louise Daugherty Panel types changed to GMS Rare Disease; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.137 | SOX9 | Eleanor Williams commented on gene: SOX9: The region upstream of SOX9 where duplications are assoicated with increased expression of KCNJ2 has been submitted to Clingen for review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia with onset in adulthood v2.0 | Louise Daugherty promoted panel to version 2.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia with onset in adulthood v1.212 | Louise Daugherty Panel types changed to GMS Rare Disease Virtual; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.137 | TRAF7 | Eleanor Williams Tag missense tag was added to gene: TRAF7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial non syndromic congenital heart disease v1.51 | TRAF7 | Eleanor Williams Tag missense tag was added to gene: TRAF7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial non syndromic congenital heart disease v1.51 | TRAF7 | Eleanor Williams Classified gene: TRAF7 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial non syndromic congenital heart disease v1.51 | TRAF7 | Eleanor Williams Added comment: Comment on list classification: Rating this gene green as 6 cases reported with missense variants in this gene with heart defects. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial non syndromic congenital heart disease v1.51 | TRAF7 | Eleanor Williams Gene: traf7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial non syndromic congenital heart disease v1.50 | TRAF7 |
Eleanor Williams gene: TRAF7 was added gene: TRAF7 was added to Familial non syndromic congenital heart disease. Sources: Literature Mode of inheritance for gene: TRAF7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TRAF7 were set to 29961569 Phenotypes for gene: TRAF7 were set to Cardiac, facial, and digital anomalies with developmental delay 618164 Review for gene: TRAF7 was set to GREEN Added comment: Associated with Cardiac, facial, and digital anomalies with developmental delay (#618164) in OMIM and Developmental Delay, Congenital Anomalies, and Dysmorphic Features in Gene2Phenotype. PMID: 29961569 - Tokita et al. 2018 - 7 cases. They report missense variants in TRAF7 in seven unrelated individuals referred for clinical exome sequencing. There was substantial phenotypic overlap between individuals, with developmental delay, congenital heart defects, limb and digital anomalies, and dysmorphic features as key features. 6 individuals had de novo variants (absence of paternal DNA in one patient did not allow confirmation of a de novo variant), with four distinct missense changes, including a c.1964G>A (p.Arg655Gln) variant in 4 individuals. The variants affect evolutionarily conserved amino acids and are located in key functional domains. Prenatal histories were notable for antenatal detection of heart anomalies (n = 3), cystic hygroma (n = 2), and two-vessel cord (n = 2). Congenital heart defects were present in six of seven patients and ranged in type and severity Sources: Literature |
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| Limb disorders v1.137 | WDPCP |
Eleanor Williams changed review comment from: PMID: 28289185 - Bruel et al 2017 - report 1 case (patient 10) with compound heterozygous variants in WDPCP and an Oral-facial-digital syndrome phenotype which includes Post-axial polydactyly of the hands and syndactyly of the feet. PMID: 27158779 - Toriyama et al 2016 - report 1 case of a 5-year-old male presenting with facial dysmorphism, tongue hamartoma, high arched palate, tooth abnormalities, and postaxial polydactyly. He was found to be compound heterozygous for two mutations in WDPCP, a frameshift and a missense variant predicted to alter splicing. Each parent had one of the variants. Functional studies in Xenopus MCCs and found that the frame-shift allele resulted in total loss of protein, while the point mutation led to a consistent but more modest defect in protein stability They also observed Y-shaped metacarpals and defects in tongue and palate morphology in Wdpcp mouse mutants PMID: 25427950 - Saari et al 2015 - report 1 case of a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas. By whole exome sequencing they found she is a compound heterozygote for a frame shift mutation and a likely pathogenic sequence variant in WDPCP. The parents and two siblings were heterozygous carriers. PMID: Kim et al 2010 - report 1 cases of a proband with a clinical diagnosis of BBS and a homozygous Fritz mutation that segregated with the disorder. Both parents and an unaffected sib were heterozygous carriers. No details 3 cases with oralfacial digitial syndrome type phenotypes and one with a clinical diagnosis of BBS.; to: PMID: 28289185 - Bruel et al 2017 - report 1 case (patient 10) with compound heterozygous variants (a missense variant and 2bp deletion leading to a frameshift) in WDPCP and an Oral-facial-digital syndrome phenotype which includes Post-axial polydactyly of the hands and syndactyly of the feet. PMID: 27158779 - Toriyama et al 2016 - report 1 case of a 5-year-old male presenting with facial dysmorphism, tongue hamartoma, high arched palate, tooth abnormalities, and postaxial polydactyly. He was found to be compound heterozygous for two mutations in WDPCP, a frameshift and a missense variant predicted to alter splicing. Each parent had one of the variants. Functional studies in Xenopus MCCs and found that the frame-shift allele resulted in total loss of protein, while the point mutation led to a consistent but more modest defect in protein stability They also observed Y-shaped metacarpals and defects in tongue and palate morphology in Wdpcp mouse mutants PMID: 25427950 - Saari et al 2015 - report 1 case of a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas. By whole exome sequencing they found she is a compound heterozygote for a frame shift mutation and a likely pathogenic sequence variant in WDPCP. The parents and two siblings were heterozygous carriers. PMID: Kim et al 2010 - report 1 cases of a proband with a clinical diagnosis of BBS and a homozygous Fritz mutation that segregated with the disorder. Both parents and an unaffected sib were heterozygous carriers. No details 3 cases with oralfacial digitial syndrome type phenotypes and one with a clinical diagnosis of BBS. |
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| Cerebral malformation v3.2 | Ellen McDonagh Changed child panels to: Holoprosencephaly; Malformations of cortical development; Neurological segmental overgrowth | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.28 |
Louise Daugherty Panel name changed from Myotonia congenita to Skeletal muscle channelopathy List of related panels changed from R76 to R76; Myotonia congenita |
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| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.184 | SMCHD1 | Ellen McDonagh changed review comment from: Comment on list classification: Promoted from Red to Amber due to overall majority of Green reviews and clinical comments from from GLH representatives.; to: Comment on list classification: Promoted from Red to Amber due to overall majority of Green reviews and clinical comments from from GLH representatives. As this is digenic, this gene has been made Amber rather than Green and tagged 'digenic'. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.137 | SDCCAG8 | Eleanor Williams Phenotypes for gene: SDCCAG8 were changed from Polydactyly; Senior-Loken syndrome 7, 613615; Bardet-Biedl syndrome 16, 615993 to Senior-Loken syndrome 7, 613615; Bardet-Biedl syndrome 16, 615993 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.136 | SDCCAG8 | Eleanor Williams Classified gene: SDCCAG8 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.136 | SDCCAG8 | Eleanor Williams Added comment: Comment on list classification: This gene is a Bardet-Biedl syndrome gene but polydactyly is not part of the phenotype - see clinical features listed in OMIM https://omim.org/entry/615993. Therefore changing the rating of this gene to red on the limb disorders panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.136 | SDCCAG8 | Eleanor Williams Gene: sdccag8 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.135 | EIF4A3 | Eleanor Williams changed review comment from: Comment on list classification: Relevant phenotype, however potential founder effect in the Brazilian population described to date. Further evidence needed therefore rating amber. Rating agreed with Genomics England clinical team.; to: Comment on list classification: Relevant phenotype, however potential founder effect in the Brazilian population described to date. The phenotype of the patient from England/Kenya is borderline for this panel. Further evidence needed therefore rating amber. Rating agreed with Genomics England clinical team. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1132 | SVBP | Rebecca Foulger Classified gene: SVBP as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1132 | SVBP | Rebecca Foulger Added comment: Comment on list classification: Updated rating to Green to match Green review by Catherine Snow. Phenotypes include global DD and intellectual disability in >3 families. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1132 | SVBP | Rebecca Foulger Gene: svbp has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1131 | PNPT1 | Rebecca Foulger commented on gene: PNPT1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1131 | PNPT1 | Rebecca Foulger Phenotypes for gene: PNPT1 were changed from Combined oxidative phosphorylation deficiency 13, 614932; Deafness, autosomal recessive 70, 614934 to Combined oxidative phosphorylation deficiency 13, 614932; Deafness, autosomal recessive 70, 614934; developmental delay; intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1131 | PNPT1 | Rebecca Foulger Publications for gene: PNPT1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.184 | POMK | Ellen McDonagh Classified gene: POMK as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.184 | POMK | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the overall reviews and comments from reviewers. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.184 | POMK | Ellen McDonagh Gene: pomk has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.183 | POLG | Ellen McDonagh Classified gene: POLG as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.183 | POLG | Ellen McDonagh Added comment: Comment on list classification: This gene will be demoted to Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.183 | POLG | Ellen McDonagh Gene: polg has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.182 | ACTA1 | Ellen McDonagh Classified gene: ACTA1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.182 | ACTA1 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.182 | ACTA1 | Ellen McDonagh Gene: acta1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.181 | AGL | Ellen McDonagh Classified gene: AGL as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.181 | AGL | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.181 | AGL | Ellen McDonagh Gene: agl has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.180 | ATP2A1 | Ellen McDonagh Classified gene: ATP2A1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.180 | ATP2A1 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.180 | ATP2A1 | Ellen McDonagh Gene: atp2a1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.179 | BVES | Ellen McDonagh changed review comment from: Comment on list classification: This gene will remain Red due to overall majority of Green reviews and clinical comments from GLH representatives.; to: Comment on list classification: This gene will remain Red due to overall majority of Red reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.179 | BVES | Ellen McDonagh Classified gene: BVES as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.179 | BVES | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.179 | BVES | Ellen McDonagh Gene: bves has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.178 | CHRND | Ellen McDonagh Classified gene: CHRND as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.178 | CHRND | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.178 | CHRND | Ellen McDonagh Gene: chrnd has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.177 | CLCN1 | Ellen McDonagh Classified gene: CLCN1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.177 | CLCN1 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.177 | CLCN1 | Ellen McDonagh Gene: clcn1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.176 | COL12A1 | Ellen McDonagh Classified gene: COL12A1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.176 | COL12A1 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.176 | COL12A1 | Ellen McDonagh Gene: col12a1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.175 | COLQ | Ellen McDonagh Classified gene: COLQ as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.175 | COLQ | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.175 | COLQ | Ellen McDonagh Gene: colq has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.174 | DNM2 | Ellen McDonagh Classified gene: DNM2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.174 | DNM2 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.174 | DNM2 | Ellen McDonagh Gene: dnm2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.173 | DUX4 | Ellen McDonagh Marked gene: DUX4 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.173 | DUX4 | Ellen McDonagh Gene: dux4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.173 | ETFDH | Ellen McDonagh Marked gene: ETFDH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.173 | ETFDH | Ellen McDonagh Gene: etfdh has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.173 | ETFDH | Ellen McDonagh Classified gene: ETFDH as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.173 | ETFDH | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.173 | ETFDH | Ellen McDonagh Gene: etfdh has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.172 | GBE1 | Ellen McDonagh Marked gene: GBE1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.172 | GBE1 | Ellen McDonagh Gene: gbe1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.172 | GBE1 | Ellen McDonagh Classified gene: GBE1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.172 | GBE1 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.172 | GBE1 | Ellen McDonagh Gene: gbe1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.171 | GFPT1 | Ellen McDonagh Classified gene: GFPT1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.171 | GFPT1 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.171 | GFPT1 | Ellen McDonagh Gene: gfpt1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.170 | GFPT1 | Ellen McDonagh Classified gene: GFPT1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.170 | GFPT1 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.170 | GFPT1 | Ellen McDonagh Gene: gfpt1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.169 | GFPT1 | Ellen McDonagh Marked gene: GFPT1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.169 | GFPT1 | Ellen McDonagh Gene: gfpt1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.169 | GYG1 | Ellen McDonagh Marked gene: GYG1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.169 | GYG1 | Ellen McDonagh Gene: gyg1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.169 | GYG1 | Ellen McDonagh Classified gene: GYG1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.169 | GYG1 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.169 | GYG1 | Ellen McDonagh Gene: gyg1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.168 | LIMS2 | Ellen McDonagh Marked gene: LIMS2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.168 | LIMS2 | Ellen McDonagh Gene: lims2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.168 | LIMS2 | Ellen McDonagh Classified gene: LIMS2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.168 | LIMS2 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on overall consensus of reviews and comments. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.168 | LIMS2 | Ellen McDonagh Gene: lims2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.167 | HNRNPDL | Ellen McDonagh Marked gene: HNRNPDL as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.167 | HNRNPDL | Ellen McDonagh Gene: hnrnpdl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.167 | HNRNPDL | Ellen McDonagh commented on gene: HNRNPDL: Removed 'watchlist tag' as this has been made Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.167 | HNRNPDL | Ellen McDonagh Tag watchlist was removed from gene: HNRNPDL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.167 | HNRNPDL | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.167 | HNRNPDL | Ellen McDonagh Mode of inheritance for gene: HNRNPDL was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.166 | HNRNPDL | Ellen McDonagh Classified gene: HNRNPDL as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.166 | HNRNPDL | Ellen McDonagh Added comment: Comment on list classification: Promoted from Amber to Green due to overall majority of Green reviews and clinical comments from GLH representatives. This gene seems to now be deemed a LGMD causative gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.166 | HNRNPDL | Ellen McDonagh Gene: hnrnpdl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.165 | ACADVL | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.165 | ACADVL | Ellen McDonagh Mode of inheritance for gene: ACADVL was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.164 | ACADVL | Ellen McDonagh Classified gene: ACADVL as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.164 | ACADVL | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.164 | ACADVL | Ellen McDonagh Gene: acadvl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.163 | BAG3 | Ellen McDonagh Marked gene: BAG3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.163 | BAG3 | Ellen McDonagh Gene: bag3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.163 | BAG3 | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.163 | BAG3 | Ellen McDonagh Mode of inheritance for gene: BAG3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.162 | BAG3 | Ellen McDonagh Classified gene: BAG3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.162 | BAG3 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.162 | BAG3 | Ellen McDonagh Gene: bag3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.161 | CASQ1 | Ellen McDonagh Classified gene: CASQ1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.161 | CASQ1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber due to expert review, however only one missense variants seems to have been reported in this gene. Awaiting further clinical input for this to be Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.161 | CASQ1 | Ellen McDonagh Gene: casq1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.160 | CPT2 | Ellen McDonagh Marked gene: CPT2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.160 | CPT2 | Ellen McDonagh Gene: cpt2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.160 | CPT2 | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.160 | CPT2 | Ellen McDonagh Mode of inheritance for gene: CPT2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.159 | CPT2 | Ellen McDonagh Classified gene: CPT2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.159 | CPT2 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.159 | CPT2 | Ellen McDonagh Gene: cpt2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.158 | CRYAB | Ellen McDonagh Classified gene: CRYAB as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.158 | CRYAB | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.158 | CRYAB | Ellen McDonagh Gene: cryab has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proteinuric renal disease v1.226 | CLCN5 | Eleanor Williams Mode of inheritance for gene: CLCN5 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.157 | DAG1 | Ellen McDonagh Marked gene: DAG1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.157 | DAG1 | Ellen McDonagh Gene: dag1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.157 | DAG1 | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.157 | DAG1 | Ellen McDonagh Mode of inheritance for gene: DAG1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.156 | DAG1 | Ellen McDonagh Classified gene: DAG1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.156 | DAG1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.156 | DAG1 | Ellen McDonagh Gene: dag1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.155 | DES | Ellen McDonagh Classified gene: DES as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.155 | DES | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.155 | DES | Ellen McDonagh Gene: des has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal tubulopathies v1.195 | SCNN1B | Eleanor Williams Added comment: Comment on mode of inheritance: Updating the mode of inheritance as both Pseudohypoaldosteronism, type I (biallelic) and Liddle syndrome 1 (monoallelic) are relevant to the panel | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal tubulopathies v1.195 | SCNN1B | Eleanor Williams Mode of inheritance for gene: SCNN1B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal tubulopathies v1.194 | SCNN1G | Eleanor Williams Added comment: Comment on mode of inheritance: Updating the MOI as both Pseudohypoaldosteronism, type I (biallelic) and Liddle syndrome 2 (monoallelic) are relevant to the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Renal tubulopathies v1.194 | SCNN1G | Eleanor Williams Mode of inheritance for gene: SCNN1G was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.154 | DOK7 | Ellen McDonagh Marked gene: DOK7 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.154 | DOK7 | Ellen McDonagh Gene: dok7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.154 | DOK7 | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.154 | DOK7 | Ellen McDonagh Mode of inheritance for gene: DOK7 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.153 | DOK7 | Ellen McDonagh Classified gene: DOK7 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.153 | DOK7 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.153 | DOK7 | Ellen McDonagh Gene: dok7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.152 | DPM3 | Ellen McDonagh Marked gene: DPM3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.152 | DPM3 | Ellen McDonagh Gene: dpm3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.152 | DPM3 | Ellen McDonagh Classified gene: DPM3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.152 | DPM3 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.152 | DPM3 | Ellen McDonagh Gene: dpm3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.151 | GNE | Ellen McDonagh Marked gene: GNE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.151 | GNE | Ellen McDonagh Gene: gne has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.151 | GNE | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.151 | GNE | Ellen McDonagh Mode of inheritance for gene: GNE was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.150 | GNE | Ellen McDonagh Classified gene: GNE as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.150 | GNE | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives, and more than 3 cases reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.150 | GNE | Ellen McDonagh Gene: gne has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.149 | ISPD | Ellen McDonagh Marked gene: ISPD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.149 | ISPD | Ellen McDonagh Gene: ispd has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.149 | ISPD | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.149 | ISPD | Ellen McDonagh Mode of inheritance for gene: ISPD was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.148 | ISPD | Ellen McDonagh Classified gene: ISPD as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.148 | ISPD | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.148 | ISPD | Ellen McDonagh Gene: ispd has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.147 | LAMA2 | Ellen McDonagh Marked gene: LAMA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.147 | LAMA2 | Ellen McDonagh Gene: lama2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.147 | LAMA2 | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.147 | LAMA2 | Ellen McDonagh Mode of inheritance for gene: LAMA2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.146 | LAMA2 | Ellen McDonagh Classified gene: LAMA2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.146 | LAMA2 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.146 | LAMA2 | Ellen McDonagh Gene: lama2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.145 | LAMP2 | Ellen McDonagh Marked gene: LAMP2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.145 | LAMP2 | Ellen McDonagh Gene: lamp2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.145 | LAMP2 | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.145 | LAMP2 | Ellen McDonagh Mode of inheritance for gene: LAMP2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.144 | LAMP2 | Ellen McDonagh Classified gene: LAMP2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.144 | LAMP2 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.144 | LAMP2 | Ellen McDonagh Gene: lamp2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.143 | LPIN1 | Ellen McDonagh Marked gene: LPIN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.143 | LPIN1 | Ellen McDonagh Gene: lpin1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.143 | LPIN1 | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.143 | LPIN1 | Ellen McDonagh Mode of inheritance for gene: LPIN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.142 | LPIN1 | Ellen McDonagh Classified gene: LPIN1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.142 | LPIN1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.142 | LPIN1 | Ellen McDonagh Gene: lpin1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.141 | MATR3 | Ellen McDonagh Marked gene: MATR3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.141 | MATR3 | Ellen McDonagh Gene: matr3 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.141 | MATR3 | Ellen McDonagh Classified gene: MATR3 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.141 | MATR3 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.141 | MATR3 | Ellen McDonagh Gene: matr3 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.140 | MYH14 | Ellen McDonagh Marked gene: MYH14 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.140 | MYH14 | Ellen McDonagh Gene: myh14 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.140 | MYH14 | Ellen McDonagh Classified gene: MYH14 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.140 | MYH14 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.140 | MYH14 | Ellen McDonagh Gene: myh14 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.139 | MYH7 | Ellen McDonagh Added comment: Comment on mode of inheritance: Changed from 'both' to monoallelic due to the publication provided by the reviewers and mode of inheritance provided in OMIM for this phenotype. To confirm with the reviewers. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.139 | MYH7 | Ellen McDonagh Mode of inheritance for gene: MYH7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.138 | MYH7 | Ellen McDonagh Classified gene: MYH7 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.138 | MYH7 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.138 | MYH7 | Ellen McDonagh Gene: myh7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.137 | NEB | Ellen McDonagh Marked gene: NEB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.137 | NEB | Ellen McDonagh Gene: neb has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.137 | NEB | Ellen McDonagh Classified gene: NEB as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.137 | NEB | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.137 | NEB | Ellen McDonagh Gene: neb has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.136 | ORAI1 | Ellen McDonagh Marked gene: ORAI1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.136 | ORAI1 | Ellen McDonagh Gene: orai1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.136 | ORAI1 | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.136 | ORAI1 | Ellen McDonagh Mode of inheritance for gene: ORAI1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.135 | ORAI1 | Ellen McDonagh Classified gene: ORAI1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.135 | ORAI1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.135 | ORAI1 | Ellen McDonagh Gene: orai1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.134 | PFKM | Ellen McDonagh Marked gene: PFKM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.134 | PFKM | Ellen McDonagh Gene: pfkm has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.134 | PFKM | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.134 | PFKM | Ellen McDonagh Mode of inheritance for gene: PFKM was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.133 | PFKM | Ellen McDonagh Classified gene: PFKM as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.133 | PFKM | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.133 | PFKM | Ellen McDonagh Gene: pfkm has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.132 | PGK1 | Ellen McDonagh Classified gene: PGK1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.132 | PGK1 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.132 | PGK1 | Ellen McDonagh Gene: pgk1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.131 | PHKA1 | Ellen McDonagh Marked gene: PHKA1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.131 | PHKA1 | Ellen McDonagh Gene: phka1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.131 | PHKA1 | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.131 | PHKA1 | Ellen McDonagh Mode of inheritance for gene: PHKA1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.130 | PHKA1 | Ellen McDonagh Classified gene: PHKA1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.130 | PHKA1 | Ellen McDonagh Gene: phka1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.129 | PHKA1 | Ellen McDonagh Classified gene: PHKA1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.129 | PHKA1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.129 | PHKA1 | Ellen McDonagh Gene: phka1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.128 | POGLUT1 | Ellen McDonagh Publications for gene: POGLUT1 were set to 27807076 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.127 | POGLUT1 | Ellen McDonagh changed review comment from: Comment on list classification: Promoted from Red to Green based on the review and comments from Chiara Marini Bettolo (NUTH).; to: Comment on list classification: Promoted from Red to Amber based on the review and comments from Chiara Marini Bettolo (NUTH), however only one variant has been reported to date. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.127 | POGLUT1 | Ellen McDonagh Classified gene: POGLUT1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.127 | POGLUT1 | Ellen McDonagh Gene: poglut1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.101 | TTN |
Zerin Hyder changed review comment from: Bryen et al: eight families with arthrogryposis multiplex congenita and myopathy bearing a TTN intron 213 extended splice-site variant (c.39974-11T>G), inherited in trans with a second pathogenic TTN variant. By Sanger sequencing the TTN gene in 31 patients from 23 families segregating congenital core myopathy and primary heart disease, Chauveau et al. (2014) identified homozygous or compound heterozygous mutations in 5 patients from 4 families. The severity of the phenotype varied among the families. All 5 patients had congenital or infantile muscle weakness with axial and distal joint contractures and relatively preserved respiratory function. One individual presented with arthrogryposis, dislocated hips with dysplasia, and elbow, hip, and knee contractures. Two families with AMC and biallelic truncating mutations in 29575618; 28040389.; to: By Sanger sequencing the TTN gene in 31 patients from 23 families segregating congenital core myopathy and primary heart disease, Chauveau et al. (2014) identified homozygous or compound heterozygous mutations in 5 patients from 4 families. The severity of the phenotype varied among the families. All 5 patients had congenital or infantile muscle weakness with axial and distal joint contractures and relatively preserved respiratory function. One individual presented with arthrogryposis, dislocated hips with dysplasia, and elbow, hip, and knee contractures. Bryen et al: eight families with arthrogryposis multiplex congenita and myopathy bearing a TTN intron 213 extended splice-site variant (c.39974-11T>G), inherited in trans with a second pathogenic TTN variant. Two families with AMC and biallelic truncating mutations in 29575618; 28040389. |
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| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.126 | POGLUT1 | Ellen McDonagh Classified gene: POGLUT1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.126 | POGLUT1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.126 | POGLUT1 | Ellen McDonagh Gene: poglut1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.125 | POMGNT2 | Ellen McDonagh Marked gene: POMGNT2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.125 | POMGNT2 | Ellen McDonagh Gene: pomgnt2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.125 | POMGNT2 | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.125 | POMGNT2 | Ellen McDonagh Mode of inheritance for gene: POMGNT2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.124 | POMGNT2 | Ellen McDonagh Classified gene: POMGNT2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.124 | POMGNT2 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.124 | POMGNT2 | Ellen McDonagh Gene: pomgnt2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.123 | PYGM | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.123 | PYGM | Ellen McDonagh Mode of inheritance for gene: PYGM was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.122 | PYGM | Ellen McDonagh Classified gene: PYGM as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.122 | PYGM | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.122 | PYGM | Ellen McDonagh Gene: pygm has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.121 | RAPSN | Ellen McDonagh Marked gene: RAPSN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.121 | RAPSN | Ellen McDonagh Gene: rapsn has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.121 | RAPSN | Ellen McDonagh Classified gene: RAPSN as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.121 | RAPSN | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.121 | RAPSN | Ellen McDonagh Gene: rapsn has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.120 | RYR1 | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.120 | RYR1 | Ellen McDonagh Mode of inheritance for gene: RYR1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.119 | RYR1 | Ellen McDonagh Marked gene: RYR1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.119 | RYR1 | Ellen McDonagh Gene: ryr1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.119 | RYR1 | Ellen McDonagh Classified gene: RYR1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.119 | RYR1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.119 | RYR1 | Ellen McDonagh Gene: ryr1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.118 | SCN4A | Ellen McDonagh Marked gene: SCN4A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.118 | SCN4A | Ellen McDonagh Gene: scn4a has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.118 | SCN4A | Ellen McDonagh Classified gene: SCN4A as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.118 | SCN4A | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.118 | SCN4A | Ellen McDonagh Gene: scn4a has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.117 | SELENON | Ellen McDonagh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.101 | SLC18A3 | Rebecca Foulger Classified gene: SLC18A3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.101 | SLC18A3 | Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber on advice from Zerin Hyder (Genomics England clinical team): 2 families with strong link to arthrogryposis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.101 | SLC18A3 | Rebecca Foulger Gene: slc18a3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.117 | SELENON | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.117 | SELENON | Ellen McDonagh Mode of inheritance for gene: SELENON was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.117 | SELENON | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.117 | SELENON | Ellen McDonagh Mode of inheritance for gene: SELENON was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.116 | SELENON | Ellen McDonagh changed review comment from: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from from GLH representatives.; to: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.116 | SELENON | Ellen McDonagh Classified gene: SELENON as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.116 | SELENON | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.116 | SELENON | Ellen McDonagh Gene: selenon has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.115 | SMCHD1 | Ellen McDonagh changed review comment from: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from from GLH representatives.; to: Comment on list classification: Promoted from Red to Amber due to overall majority of Green reviews and clinical comments from from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.115 | SMCHD1 | Ellen McDonagh Classified gene: SMCHD1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.115 | SMCHD1 | Ellen McDonagh Gene: smchd1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.114 | SMCHD1 | Ellen McDonagh Classified gene: SMCHD1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.114 | SMCHD1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.114 | SMCHD1 | Ellen McDonagh Gene: smchd1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.113 | SMCHD1 | Ellen McDonagh Tag digenic tag was added to gene: SMCHD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.113 | SMN1 | Ellen McDonagh Marked gene: SMN1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.113 | SMN1 | Ellen McDonagh Gene: smn1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.113 | SMN1 | Ellen McDonagh Added comment: Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.113 | SMN1 | Ellen McDonagh Mode of inheritance for gene: SMN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.112 | SMN1 | Ellen McDonagh Classified gene: SMN1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.112 | SMN1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.112 | SMN1 | Ellen McDonagh Gene: smn1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.111 | STIM1 | Ellen McDonagh Marked gene: STIM1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.111 | STIM1 | Ellen McDonagh Gene: stim1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.111 | STIM1 | Ellen McDonagh Classified gene: STIM1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.111 | STIM1 | Ellen McDonagh Gene: stim1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.110 | STIM1 | Ellen McDonagh Classified gene: STIM1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.110 | STIM1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green based on review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.110 | STIM1 | Ellen McDonagh Gene: stim1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.109 | SYNE2 | Ellen McDonagh Classified gene: SYNE2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.109 | SYNE2 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall majority of Green reviews and clinical comments from from GLH representatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.109 | SYNE2 | Ellen McDonagh Gene: syne2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.108 | TPM3 | Ellen McDonagh changed review comment from: Comment on list classification: Gene to be kept Red until further evidence for this to be appropriate on this panel.; to: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.108 | TPM2 | Ellen McDonagh changed review comment from: Comment on list classification: Gene to be kept Red until further evidence for this to be appropriate on this panel.; to: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.108 | TNNT3 | Ellen McDonagh changed review comment from: Comment on list classification: This gene will remain Red based on Chiara Marini Bettolo (NUTH) until further evidence for this to be appropriate on this panel.; to: Comment on list classification: This gene will remain Red based on the review and comments from Chiara Marini Bettolo (NUTH). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.108 | TNNT3 | Ellen McDonagh Classified gene: TNNT3 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.108 | TNNT3 | Ellen McDonagh Added comment: Comment on list classification: This gene will remain Red based on Chiara Marini Bettolo (NUTH) until further evidence for this to be appropriate on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.108 | TNNT3 | Ellen McDonagh Gene: tnnt3 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.107 | TNPO3 | Ellen McDonagh Classified gene: TNPO3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.107 | TNPO3 | Ellen McDonagh Gene: tnpo3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.106 | TNPO3 | Ellen McDonagh Classified gene: TNPO3 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.106 | TNPO3 | Ellen McDonagh Added comment: Comment on list classification: Based on expert review from Chiara Marini Bettolo (NUTH), this gene has been promoted from Red to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.106 | TNPO3 | Ellen McDonagh Gene: tnpo3 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.100 | TOR1AIP1 | Rebecca Foulger Classified gene: TOR1AIP1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.100 | TOR1AIP1 | Rebecca Foulger Added comment: Comment on list classification: One family (PMID:24856141) supports a Red rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.100 | TOR1AIP1 | Rebecca Foulger Gene: tor1aip1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.99 | TOR1AIP1 |
Rebecca Foulger gene: TOR1AIP1 was added gene: TOR1AIP1 was added to Arthrogryposis. Sources: Literature,Other Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TOR1AIP1 were set to 24856141 Phenotypes for gene: TOR1AIP1 were set to joint contractures; ?Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures, 617072 Added comment: Added TOR1AIP1 to panel based on Amber rating on R266 Neuromuscular arthrogryposis panel, and PMID:24856141 2014 paper who report a consanguineous Turkish family with muscle weakness, atrophy and joint contractures in three affected individuals (2 siblings and a cousin). They all had a homozygous variant in TOR1AIP1 (c.186delG causing a premature stop codon). Healthy parents were heterozygous carriers, and allele segregation in the family supported recessive inheritance. Sources: Literature, Other |
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| Arthrogryposis v2.98 | SLC18A3 | Rebecca Foulger Added comment: Comment on publications: PMID:27590285: report individuals from 2 families with biallelic SLC18A3 variants and presynaptic congenital myasthenic syndrome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.98 | SLC18A3 | Rebecca Foulger Publications for gene: SLC18A3 were set to 28188302; 27590285; 31059209 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.97 | SLC18A3 | Rebecca Foulger commented on gene: SLC18A3: PMID:28188302 (Aran et al., 2017) report 2 brothers from a nonconsanguineous Yemeni Jewish family manifested at birth with severe hypotonia and arthrogryposis. The brothers were homozygous for missense variant in SLC18A3 c.1078G>C, p.Gly360Arg. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.97 | SLC18A3 | Rebecca Foulger commented on gene: SLC18A3: PMID:31059209 (Hakonen et al., 2019) report 2 sibling Finnish fetuses with with fetal akinesia, arthrogryposis, edema, and partial cleft palate and a homozygous variant in SLC18A3: c.1116C>A, p.(Cys372Ter). The parents were distant relatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.97 | SLC18A3 | Rebecca Foulger Classified gene: SLC18A3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.97 | SLC18A3 | Rebecca Foulger Gene: slc18a3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.96 | SLC18A3 |
Rebecca Foulger gene: SLC18A3 was added gene: SLC18A3 was added to Arthrogryposis. Sources: Other,Literature Mode of inheritance for gene: SLC18A3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC18A3 were set to 28188302; 27590285; 31059209 Phenotypes for gene: SLC18A3 were set to Myasthenic syndrome, congenital, 21, presynaptic, 617239; arthrogryposis Added comment: Added to panel based on Amber rating on Neuromuscular arthrogryposis panel V0.21 and literature evidence supporting an Arthrogryposis phenotype. Sources: Other, Literature |
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| Skeletal ciliopathies v0.42 | WDPCP | Eleanor Williams Classified gene: WDPCP as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.42 | WDPCP | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.42 | WDPCP | Eleanor Williams Gene: wdpcp has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.41 | TTC8 | Eleanor Williams Classified gene: TTC8 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.41 | TTC8 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.41 | TTC8 | Eleanor Williams Gene: ttc8 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.40 | TRIM32 | Eleanor Williams Classified gene: TRIM32 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.40 | TRIM32 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.40 | TRIM32 | Eleanor Williams Gene: trim32 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.39 | SDCCAG8 | Eleanor Williams Classified gene: SDCCAG8 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.39 | SDCCAG8 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.39 | SDCCAG8 | Eleanor Williams Gene: sdccag8 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.38 | MKS1 | Eleanor Williams Classified gene: MKS1 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.38 | MKS1 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.38 | MKS1 | Eleanor Williams Gene: mks1 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.105 | TPM2 | Ellen McDonagh Classified gene: TPM2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.105 | TPM2 | Ellen McDonagh Added comment: Comment on list classification: Gene to be kept Red until further evidence for this to be appropriate on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.105 | TPM2 | Ellen McDonagh Gene: tpm2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.37 | MKKS | Eleanor Williams Classified gene: MKKS as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.37 | MKKS | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.37 | MKKS | Eleanor Williams Gene: mkks has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.36 | LZTFL1 | Eleanor Williams Classified gene: LZTFL1 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.36 | LZTFL1 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.36 | LZTFL1 | Eleanor Williams Gene: lztfl1 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.104 | TPM3 | Ellen McDonagh Classified gene: TPM3 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.104 | TPM3 | Ellen McDonagh Added comment: Comment on list classification: Gene to be kept Red until further evidence for this to be appropriate on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.104 | TPM3 | Ellen McDonagh Gene: tpm3 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.35 | IFT74 | Eleanor Williams Classified gene: IFT74 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.35 | IFT74 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.35 | IFT74 | Eleanor Williams Gene: ift74 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.34 | IFT27 | Eleanor Williams Classified gene: IFT27 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.34 | IFT27 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.34 | IFT27 | Eleanor Williams Gene: ift27 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.33 | CCDC28B | Eleanor Williams Classified gene: CCDC28B as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.33 | CCDC28B | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.33 | CCDC28B | Eleanor Williams Gene: ccdc28b has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.103 | TTN | Ellen McDonagh Mode of pathogenicity for gene: TTN was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.32 | C8orf37 | Eleanor Williams Classified gene: C8orf37 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.32 | C8orf37 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.32 | C8orf37 | Eleanor Williams Gene: c8orf37 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.31 | BBS9 | Eleanor Williams Classified gene: BBS9 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.31 | BBS9 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.31 | BBS9 | Eleanor Williams Gene: bbs9 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.30 | BBS7 | Eleanor Williams Classified gene: BBS7 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.30 | BBS7 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.30 | BBS7 | Eleanor Williams Gene: bbs7 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.102 | TTN | Ellen McDonagh Classified gene: TTN as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.102 | TTN | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to overall the majority of reviews are Green, and there is a consensus that although classifying variants in this is difficult, additional phenotyping studies can aid in confirmation of diagnosis and that this gene should be included on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.102 | TTN | Ellen McDonagh Gene: ttn has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.29 | BBS5 | Eleanor Williams Classified gene: BBS5 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.29 | BBS5 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.29 | BBS5 | Eleanor Williams Gene: bbs5 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.28 | BBS4 | Eleanor Williams Classified gene: BBS4 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.28 | BBS4 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.28 | BBS4 | Eleanor Williams Gene: bbs4 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.27 | BBS2 | Eleanor Williams Classified gene: BBS2 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.27 | BBS2 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.27 | BBS2 | Eleanor Williams Gene: bbs2 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.26 | BBS12 | Eleanor Williams Classified gene: BBS12 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.26 | BBS12 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.26 | BBS12 | Eleanor Williams Gene: bbs12 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.25 | BBS10 | Eleanor Williams Classified gene: BBS10 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.25 | BBS10 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.25 | BBS10 | Eleanor Williams Gene: bbs10 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.24 | BBS1 | Eleanor Williams Classified gene: BBS1 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.24 | BBS1 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.24 | BBS1 | Eleanor Williams Gene: bbs1 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.23 | BBIP1 | Eleanor Williams Classified gene: BBIP1 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.23 | BBIP1 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.23 | BBIP1 | Eleanor Williams Gene: bbip1 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.22 | ARL6 | Eleanor Williams Classified gene: ARL6 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.22 | ARL6 | Eleanor Williams Added comment: Comment on list classification: Removing from the skeletal ciliopathies panel as it is covered by the Bardet Biedl syndrome panel (panel ID: 543) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.22 | ARL6 | Eleanor Williams Gene: arl6 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.101 | VMA21 | Ellen McDonagh Classified gene: VMA21 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.101 | VMA21 | Ellen McDonagh Added comment: Comment on list classification: Promoted to Green due to consensus from reviewers and submitted gene lists from GLHs. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.101 | VMA21 | Ellen McDonagh Gene: vma21 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.95 |
Rebecca Foulger List of related panels changed from Arthrogrythsis to Arthrogrythsis; R83 Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual |
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| Early onset or syndromic epilepsy v1.497 | Rebecca Foulger Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pigmentary skin disorders v0.20 | PMS2 | Catherine Snow Added comment: Comment on mode of inheritance: Comment on mode of inheritance: Advice from clinical team to change PMS2 from Monoallelic to Biallelic. Biallelic form exhibits relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pigmentary skin disorders v0.20 | PMS2 | Catherine Snow Mode of inheritance for gene: PMS2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pigmentary skin disorders v0.19 | MSH6 | Catherine Snow Added comment: Comment on mode of inheritance: Comment on mode of inheritance: Advice from clinical team to change MSH6 from Monoallelic to Biallelic. Biallelic form exhibits relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pigmentary skin disorders v0.19 | MSH6 | Catherine Snow Mode of inheritance for gene: MSH6 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pigmentary skin disorders v0.18 | MSH2 | Catherine Snow Added comment: Comment on mode of inheritance: Comment on mode of inheritance: Advice from clinical team to change MSH2 from Monoallelic to Biallelic. Biallelic form exhibits relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pigmentary skin disorders v0.18 | MSH2 | Catherine Snow Mode of inheritance for gene: MSH2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pigmentary skin disorders v0.17 | MLH1 | Catherine Snow Added comment: Comment on mode of inheritance: Comment on mode of inheritance: Advice from clinical team to change MLH1 from Monoallelic to Biallelic. Biallelic form exhibits relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pigmentary skin disorders v0.17 | MLH1 | Catherine Snow Mode of inheritance for gene: MLH1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.117 | TAF1 | Louise Daugherty changed review comment from: Comment on list classification: Prior to GLH sign off for this panel, TAF1 was discussed further by the specialist test group. It was raised by WWMGLH that the gene should be downgraded from Green to Red as they were not sure if the pipeline could detect the alu-like insertion variant - and no other variants reported in HGMDPro in association with Dystonia-Parkinsonism. However, further correspondence from LNGLH Huw Morris suggested Amber rating - as per movement disorders on PanelApp. Noting that the genetic aetiology of this disorder is complex and not fully understood; to: Comment on list classification: Prior to GLH sign off for this panel, TAF1 was discussed further by the specialist test group. It was raised by WWMGLH that the gene should be downgraded from Green to Red as they were not sure if the pipeline could detect the alu-like insertion variant - and no other variants reported in HGMDPro in association with Dystonia-Parkinsonism. However, further correspondence from LNGLH Huw Morris suggested an Amber rating - as per movement disorders on PanelApp. Noting that the genetic aetiology of this disorder is complex and not fully understood. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.117 | TAF1 | Louise Daugherty Classified gene: TAF1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.117 | TAF1 | Louise Daugherty Added comment: Comment on list classification: Prior to GLH sign off for this panel, TAF1 was discussed further by the specialist test group. It was raised by WWMGLH that the gene should be downgraded from Green to Red as they were not sure if the pipeline could detect the alu-like insertion variant - and no other variants reported in HGMDPro in association with Dystonia-Parkinsonism. However, further correspondence from LNGLH Huw Morris suggested Amber rating - as per movement disorders on PanelApp. Noting that the genetic aetiology of this disorder is complex and not fully understood | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.117 | TAF1 | Louise Daugherty Gene: taf1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pigmentary skin disorders v0.16 | PALB2 | Catherine Snow Added comment: Comment on mode of inheritance: Advice from clinical team to change PALB2 from Monoallelic to Biallelic. Biallelic form exhibits relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pigmentary skin disorders v0.16 | PALB2 | Catherine Snow Mode of inheritance for gene: PALB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.496 | WWOX | Rebecca Foulger Publications for gene: WWOX were set to Tabarki (2015) Ben-Salam (2015) Mignot (2015) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.495 | WWOX | Rebecca Foulger Phenotypes for gene: WWOX were changed from to Epileptic encephalopathy, early infantile, 28, 616211 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.494 | WDR45 | Rebecca Foulger Phenotypes for gene: WDR45 were changed from to Neurodegeneration with brain iron accumulation 5, 300894 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.493 | WDR45 | Rebecca Foulger Publications for gene: WDR45 were set to Saitsu et al (2013) Nat Genet. 45(4):445-9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.492 | STX1B | Rebecca Foulger Phenotypes for gene: STX1B were changed from to Generalized epilepsy with febrile seizures plus, type 9, 616172 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.491 | STX1B | Rebecca Foulger Mode of inheritance for gene: STX1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.490 | SLC6A1 | Rebecca Foulger Phenotypes for gene: SLC6A1 were changed from to Myoclonic-atonic epilepsy, 616421 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.116 | TAF1 | Louise Daugherty Tag sva was removed from gene: TAF1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.489 | SLC6A1 | Rebecca Foulger Publications for gene: SLC6A1 were set to Carvill et al (2015) Am J Hum Genet 96(5): 808-15 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.116 | MARS2 | Louise Daugherty Classified gene: MARS2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.116 | MARS2 | Louise Daugherty Added comment: Comment on list classification: Prior to GLH sign off for this panel, MARS2 was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to upgrade this gene to Amber as the the evidence of a primary phenotype associated with this indication (dementia/ALS/Parkinsonism), was not strong enough to rate MARS2 Green. The difficulty of detecting the rearrangements by WGS was also raised so agreed to make Amber | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.116 | MARS2 | Louise Daugherty Gene: mars2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.488 | PNPO | Rebecca Foulger Phenotypes for gene: PNPO were changed from to Pyridoxamine 5'-phosphate oxidase deficiency, 610090 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.487 | NDUFS8 | Rebecca Foulger Phenotypes for gene: NDUFS8 were changed from Mitochondrial complex I deficiency, nuclear type 2, 618222 to Mitochondrial complex I deficiency, nuclear type 2, 618222; Leigh syndrome due to mitochondrial complex I deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.486 | NDUFS8 | Rebecca Foulger Phenotypes for gene: NDUFS8 were changed from to Mitochondrial complex I deficiency, nuclear type 2, 618222 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.485 | DNM1 | Rebecca Foulger Mode of inheritance for gene: DNM1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.484 | DNM1 | Rebecca Foulger Publications for gene: DNM1 were set to EuroEPINOMICS-RES Consortium (2014) AJHG 95:1-11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.483 | DNM1 | Rebecca Foulger Phenotypes for gene: DNM1 were changed from to Epileptic encephalopathy, early infantile, 31, 616346 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.482 | CYFIP2 | Rebecca Foulger Mode of pathogenicity for gene: CYFIP2 was changed from None to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.481 | CYFIP2 | Rebecca Foulger Publications for gene: CYFIP2 were set to 29534297 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.480 | CYFIP2 | Rebecca Foulger Phenotypes for gene: CYFIP2 were changed from to Epileptic encephalopathy, early infantile, 65, 618008 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.479 | CSTB | Rebecca Foulger Publications for gene: CSTB were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.478 | CSTB | Rebecca Foulger Phenotypes for gene: CSTB were changed from to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.115 | ITM2B |
Louise Daugherty commented on gene: ITM2B: Prior to GLH sign off for this panel, ITM2B was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to keep this gene Green. It was highlighted that two fs variants and one missense rated red on HGMDpro - missense likely pathogenic using in silico tools only. Second amber rated missense in association with dementia. Only 2 cases with segregation - so it was suggested the gene should be Amber not Green. However, further feedback confirmed the Green rating as it was noted that this is rare, but there are a couple of families with a stop-loss mutation in this gene reported in one of the labs, so should remain green. |
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| Skeletal dysplasia v1.254 | PAX3 | Eleanor Williams Classified gene: PAX3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.254 | PAX3 | Eleanor Williams Added comment: Comment on list classification: Changing the rating from red to green as there is evidence for association with cranofacial and limb phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.254 | PAX3 | Eleanor Williams Gene: pax3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.253 | PAX3 | Eleanor Williams Publications for gene: PAX3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.252 | PAX3 | Eleanor Williams Phenotypes for gene: PAX3 were changed from Craniofacial-Deafness-Hand Syndrome to Craniofacial-deafness-hand syndrome, 122880; Waardenburg syndrome, type 1, 193500; Waardenburg syndrome, type 3, 148820 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.115 | DAB1 | Louise Daugherty Classified gene: DAB1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.115 | DAB1 | Louise Daugherty Added comment: Comment on list classification: Prior to GLH sign off for this panel, DAB1 was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to downgrade this gene from Amber to Red. . Several cases - ATTTC 31-75n embedded within an ATTTT repeat. Unlikely to be picked up by WGS - Red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.115 | DAB1 | Louise Daugherty Gene: dab1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.114 | DAB1 | Louise Daugherty Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.114 | DAB1 | Louise Daugherty changed review comment from: Prior to GLH sign off for this panel, DAB1 was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to downgrade this gene from Amber to Red. . Several cases - ATTTC 31-75n embedded within an ATTTT repeat. Unlikely to be picked up by WGS - Red; to: Prior to GLH sign off for this panel, DAB1 was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to downgrade this gene from Amber to Red. . Several cases - ATTTC 31-75n embedded within an ATTTT repeat. Unlikely to be picked up by WGS - Red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.114 | DAB1 | Louise Daugherty commented on gene: DAB1: Prior to GLH sign off for this panel, DAB1 was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to downgrade this gene from Amber to Red. . Several cases - ATTTC 31-75n embedded within an ATTTT repeat. Unlikely to be picked up by WGS - Red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.251 | PAX3 | Eleanor Williams Added comment: Comment on mode of inheritance: Waardenburg syndrome, type 3 is both AD and AR in OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.251 | PAX3 | Eleanor Williams Mode of inheritance for gene: PAX3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.250 | PAX3 | Eleanor Williams edited their review of gene: PAX3: Added comment: Comment from Tracy Lester - PAX3 should be made green on the skeletal dysplasia panel in the absence of any other relevant panel in the test directory. It is currently red on the Craniosynostosis panel.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.114 | CLP1 | Louise Daugherty Classified gene: CLP1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.114 | CLP1 | Louise Daugherty Added comment: Comment on list classification: Prior to GLH sign off for this panel, CLP1 was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to downgrade this gene from Amber to Red. Pontocerebellar hypoplasia type 10 - childhood onset so red. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.114 | CLP1 | Louise Daugherty Gene: clp1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.250 | PAX3 | Eleanor Williams commented on gene: PAX3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.113 | ATP8A2 | Louise Daugherty Classified gene: ATP8A2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.113 | ATP8A2 | Louise Daugherty Added comment: Comment on list classification: Prior to GLH sign off for this panel, ATP8A2 was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to downgrade this gene from Amber to Red. It was noted that it is assoicated to cerebellar ataxia, MR and dysequilibrium syndrome type 4. Guissart et al 2019 J Neuro PMID: 31612321 - plus review of 26 previously reported cases. All have onset in childhood – so recommended Red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.113 | ATP8A2 | Louise Daugherty Gene: atp8a2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.112 | ATP8A2 | Louise Daugherty Publications for gene: ATP8A2 were set to 22892528; 27679995; 2845499 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.111 | ATP8A2 | Louise Daugherty changed review comment from: Comment on list classification: Prior to GLH sign off for this panel, ATP8A2 was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to downgrade this gene from Amber to Red.; to: Comment on list classification: Prior to GLH sign off for this panel, ATP8A2 was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to downgrade this gene from Amber to Red. ATP8A2 Cerebellar ataxia, MR and dysequilibrium syndrome type 4. Guissart et al 2019 J Neuro PMID: 31612321 - plus review of 26 previously reported cases. All have onset in childhood- red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.111 | ATP8A2 | Louise Daugherty Classified gene: ATP8A2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.111 | ATP8A2 | Louise Daugherty Added comment: Comment on list classification: Prior to GLH sign off for this panel, ATP8A2 was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to downgrade this gene from Amber to Red. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.111 | ATP8A2 | Louise Daugherty Gene: atp8a2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.110 | ARX | Louise Daugherty Classified gene: ARX as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.110 | ARX | Louise Daugherty Added comment: Comment on list classification: Prior to GLH sign off for this panel, ARX was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to downgrade this gene from Amber to Red. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.110 | ARX | Louise Daugherty Gene: arx has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.109 | AP5Z1 | Louise Daugherty commented on gene: AP5Z1: Prior to GLH sign off for this panel, AP5Z1 was discussed further by the specialist test group. It was agreed by all GLHs (Wessex and West Midlands GLH, Yorkshire and North East GLH, London North GLH) to keep this gene rated as Amber because there can be Parkinsonism and cognitive impairment, but not Green as not primary phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.363 | Rebecca Foulger List of related panels changed from R21 to R21; Fetal anomalies with a likely genetic cause | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.362 | KLF1 | Rebecca Foulger Phenotypes for gene: KLF1 were changed from ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE IV to ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE IV; Hydrops Fetalis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.361 | KLF1 | Rebecca Foulger Publications for gene: KLF1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.360 | KLF1 | Rebecca Foulger Mode of pathogenicity for gene: KLF1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.359 | KLF1 | Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from 'Monoallelic' to 'BOTH AD+AR' (after agreement from Rhiannon Mellis, GOSH), to match the MOI on the Fetal hydrops v.1.16 panel. The expanded MOI is based on compound heterozygous cases in PMID:25724378 and PMID:28361594. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.359 | KLF1 | Rebecca Foulger Mode of inheritance for gene: KLF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.250 | IL11RA | Eleanor Williams commented on gene: IL11RA: Comment from Tracy Lester - IL11RA should stay on the skeletal dysplasia panel in the absence of a specific craniofacial panel. Some patients also display minor digit anomalies, such as syndactyly and/or clinodactyly. Cases can have midface hypoplasia and other craniofacial signs without clinical CSS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.250 | TGFBR1 | Eleanor Williams changed review comment from: Comment on list classification: Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester). It is green on the Craniosynostosis and Ehlers Danlos panels.; to: Comment on list classification: Suggested by Rhoda Akilapa for removal. Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester). It is green on the Craniosynostosis and Ehlers Danlos panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.250 | IGF1R | Eleanor Williams Classified gene: IGF1R as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.250 | IGF1R | Eleanor Williams Added comment: Comment on list classification: Suggested by Rhoda Akilapa for removal. Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester) that there is no major skeletal involvement. It is green on microcephaly and growth failure panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.250 | IGF1R | Eleanor Williams Gene: igf1r has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.249 | EFNB1 | Eleanor Williams Classified gene: EFNB1 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.249 | EFNB1 | Eleanor Williams Added comment: Comment on list classification: Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester) that it is a predominantly craniosynostosis phenotype. It is green on the Craniosynostosis panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.249 | EFNB1 | Eleanor Williams Gene: efnb1 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.248 | ZIC1 | Eleanor Williams Classified gene: ZIC1 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.248 | ZIC1 | Eleanor Williams Added comment: Comment on list classification: Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester) that there is no major skeletal involvement. It is green on the Craniosynostosis panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.248 | ZIC1 | Eleanor Williams Gene: zic1 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.247 | TGFBR1 | Eleanor Williams Classified gene: TGFBR1 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.247 | TGFBR1 | Eleanor Williams Added comment: Comment on list classification: Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester). It is green on the Craniosynostosis and Ehlers Danlos panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.247 | TGFBR1 | Eleanor Williams Gene: tgfbr1 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.246 | TCOF1 | Eleanor Williams commented on gene: TCOF1: Comment from Tracy Lester - TCOF1 should stay on the skeletal dysplasia panel in the absence of a specific craniofacial panel. It is currently red on the Craniosynostosis panel (https://panelapp.genomicsengland.co.uk/panels/168/gene/TCOF1/) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.246 | TCF12 | Eleanor Williams Classified gene: TCF12 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.246 | TCF12 | Eleanor Williams Added comment: Comment on list classification: Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester) that there is no major skeletal involvement. It is green on the Craniosynostosis panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.246 | TCF12 | Eleanor Williams Gene: tcf12 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.245 | KAT6A | Eleanor Williams Classified gene: KAT6A as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.245 | KAT6A | Eleanor Williams Added comment: Comment on list classification: Making this gene grey as there is agreement from GMS musculoskeletal group (Tracy Lester) that there is no major skeletal involvement. It is green on the Craniosynostosis panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.245 | KAT6A | Eleanor Williams Gene: kat6a has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.244 | ALX4 | Eleanor Williams commented on gene: ALX4: Comment from Tracy Lester - ALX4 should stay on the skeletal dysplasia panel in the absence of a specific craniofacial panel. It is currently green on the Craniosynostosis panel because GOF variants can have a craniosynostosis phenotype (https://panelapp.genomicsengland.co.uk/panels/168/gene/ALX4/). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.244 | ALX1 | Eleanor Williams commented on gene: ALX1: Comment from Tracy Lester - ALX1 should stay on the skeletal dysplasia panel in the absence of a specific craniofacial panel. It is currently red on the Craniosynostosis panel (https://panelapp.genomicsengland.co.uk/panels/168/gene/ALX1/) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.244 | ALX3 | Eleanor Williams commented on gene: ALX3: Comment from Tracy Lester - ALX3 should stay on the skeletal dysplasia panel in the absence of a specific craniofacial panel. It is currently red on the Craniosynostosis panel (https://panelapp.genomicsengland.co.uk/panels/168/gene/ALX3/) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypotonic infant v3.1098 | Rebecca Foulger List of related panels changed from Floppy infant with a likely central cause; Hypotonic infant to Floppy infant with a likely central cause; Hypotonic infant; R69 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.45 | ANK2 | Matthew Edwards changed review comment from: Gene on Royal Brompton diagnostic panel. Only VUS reported from our lab. Good evidence for association with arrhythmia phenotypes rather than classic LQTS, but gene should exist on this panel as well as larger arrhythmia panel due to possible clinical overlap/differential diagnosis; to: Gene on Royal Brompton diagnostic panel. Only VUS reported from our lab. Limited evidence for association with arrhythmia phenotypes rather than classic LQTS, and likely only rare LOF causative. But gene should possibly exist on this panel as well as larger arrhythmia panel due to possible clinical overlap/differential diagnosis? | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.358 | CRYBB1 | Rebecca Foulger Phenotypes for gene: CRYBB1 were changed from CATARACT, CONGENITAL NUCLEAR, AUTOSOMAL RECESSIVE 3 to CATARACT 17, MULTIPLE TYPES; CATARACT 17, MULTIPLE TYPES, MONOALLELIC; CATARACT, CONGENITAL NUCLEAR, AUTOSOMAL RECESSIVE 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.357 | CRYBB1 | Rebecca Foulger Added comment: Comment on mode of inheritance: Although the 'confirmed' disorder in DDG2P has 'monoallelic' inheritance (and 'probable' rating for the biallelic disorders), have kept the MOI as 'both AD and AR' on the fetal panel so all cataract cases are picked up. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.357 | CRYBB1 | Rebecca Foulger Mode of inheritance for gene: CRYBB1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.175 | EDAR | Rebecca Foulger Added comment: Comment on phenotypes: Added new DDG2P disorder to phenotypes: ECTODERMAL DYSPLASIA 10A, HYPOHIDROTIC/HAIR/NAIL TYPE, AUTOSOMAL DOMINANT;Ectodermal dysplasia 10B. DDG2P rating: confirmed. Allelic requirement: monoallelic. Mutation consequence: dominant negative. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.175 | EDAR | Rebecca Foulger Phenotypes for gene: EDAR were changed from Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive to ECTODERMAL DYSPLASIA 10A, HYPOHIDROTIC/HAIR/NAIL TYPE, AUTOSOMAL DOMINANT; Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.174 | EDAR | Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from 'BIALLELIC' to 'BOTH AD+AR' to match recent DDG2P update, and to be consistent with OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.174 | EDAR | Rebecca Foulger Mode of inheritance for gene: EDAR was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.173 | USP7 | Rebecca Foulger Classified gene: USP7 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.173 | USP7 | Rebecca Foulger Gene: usp7 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.172 | USP7 | Rebecca Foulger Phenotypes for gene: USP7 were changed from Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism to USP7-related developmental disorder (monoallelic); Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.171 | USP7 | Rebecca Foulger Tag watchlist tag was added to gene: USP7. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.171 | USP7 | Rebecca Foulger commented on gene: USP7: Added 'watchlist' tag to highlight different G2P ratings for different disorders. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.171 | USP7 |
Rebecca Foulger commented on gene: USP7: Updated rating from Red to Amber to match current DDG2P ratings: probable for USP7-related developmental disorder (monoallelic): monoallelic, loss of function. possible for Intellectual disability, autism, epilepsy, aggressive behaviour, hypotonia, and hypogonadism: no MOI, no MOP. |
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| DDG2P v1.171 | SMAD4 | Rebecca Foulger commented on gene: SMAD4: Added 'watchlist' tag to highlight different G2P ratings for different disorders. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.171 | SMAD4 | Rebecca Foulger Tag watchlist tag was added to gene: SMAD4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.171 | SCN11A | Rebecca Foulger Tag watchlist tag was added to gene: SCN11A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.171 | NUP107 | Rebecca Foulger Tag watchlist tag was added to gene: NUP107. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.171 | NUP107 | Rebecca Foulger commented on gene: NUP107: Added 'watchlist' tag to highlight different G2P ratings for different disorders. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.171 | KDM6B | Rebecca Foulger Mode of pathogenicity for gene: KDM6B was changed from Other - please provide details in the comments to None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.170 | KDM6B | Rebecca Foulger Phenotypes for gene: KDM6B were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to AUTOSOMAL RECESSIVE MENTAL RETARDATION; KDM6B-related developmental disorder (monoallelic) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.169 | KDM6B | Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from BIALLELIC to MONOALLELIC to match MOI of disorder with highest rating (KDM6B-related developmental disorder (monoallelic)). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.169 | KDM6B | Rebecca Foulger Mode of inheritance for gene: KDM6B was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.168 | KDM6B | Rebecca Foulger Classified gene: KDM6B as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.168 | KDM6B | Rebecca Foulger Gene: kdm6b has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.167 | KDM6B |
Rebecca Foulger commented on gene: KDM6B: Updated rating from Red to Amber to match current DDG2P ratings: DDG2P rating of probable for KDM6B-related developmental disorder (monoallelic): monoallelic, loss of function. DDG2P rating of possible for AUTOSOMAL RECESSIVE MENTAL RETARDATION: biallelic, all missense/in frame. |
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| Intellectual disability v2.1129 | PNPT1 |
Konstantinos Varvagiannis changed review comment from: Biallelic PNPT1 pathogenic variants cause Combined oxidative phosphorylation deficiency 13 (MIM 614932). Despite phenotypic variability - common to disorders resulting from mitochondrial dysfunction - DD and ID of relevant severity to the current panel have been reported in several individuals published in the literature. Seizures may also be observed. Rius et al (2019 - PMID: 31752325) provide an overview of 24 affected individuals (7 new and 17 from previous studies). Neurodevelopmental features are summarized in fig.1 and additional details are provided in the supplement. Based on this review, seizures were present in 7 individuals (of the 18 for whom this information was available). PNPT1 encodes the mitochondrial polynucleotide phosphorylase, involved in the import of nuclear-encoded RNA to mitochondria. Loss of its activity has been shown to result in combined respiratory chain deficiency. However, as discussed by Rius et al and previous articles as well, OXPHOS studies in affected individuals may be normal or suggestive of only mild impairement due to tissue specificity and different assay methods used (eg. spectrophotometric vs dipstick activity assays). The same applies to lactate which was normal or mildly elevated in some affected individuals. Missense, pLoF function variants as well as a synonymous one leading to aberrant splicing (NM_033109.4:c.1818T>G) have been reported. Overall, this gene might be considered for upgrade to green rating.; to: Biallelic PNPT1 pathogenic variants cause Combined oxidative phosphorylation deficiency 13 (MIM 614932). Despite phenotypic variability - common to disorders resulting from mitochondrial dysfunction - DD and ID of relevant severity to the current panel have been reported in several individuals published in the literature. Seizures may also be observed. Rius et al (2019 - PMID: 31752325) provide an overview of 24 affected individuals (7 new and 17 from previous studies). Neurodevelopmental features are summarized in fig.1 and additional details are provided in the supplement. Based on this review, seizures were present in 7 individuals (of the 18 for whom this information was available). PNPT1 encodes the mitochondrial polynucleotide phosphorylase, involved in the import of nuclear-encoded RNA to mitochondria. Loss of its activity has been shown to result in combined respiratory chain deficiency. However, as discussed by Rius et al and previous articles as well, OXPHOS studies in affected individuals may be normal or suggestive of only mild impairment due to tissue specificity and different assay methods used (eg. spectrophotometric vs dipstick activity assays). The same applies to lactate which was normal or mildly elevated in some affected individuals. Missense, pLoF function variants as well as a synonymous one leading to aberrant splicing (NM_033109.4:c.1818T>G) have been reported. Overall, this gene might be considered for upgrade to green rating. |
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| Early onset or syndromic epilepsy v1.477 | PNPT1 |
Konstantinos Varvagiannis gene: PNPT1 was added gene: PNPT1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: PNPT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNPT1 were set to 31752325 Phenotypes for gene: PNPT1 were set to Combined oxidative phosphorylation deficiency 13, MIM 614932 Penetrance for gene: PNPT1 were set to Complete Review for gene: PNPT1 was set to GREEN Added comment: Reviewed for the intellectual disability panel. Seizures may be observed in affected individuals (details below). Please consider inclusion with amber / green rating. --- Biallelic PNPT1 pathogenic variants cause Combined oxidative phosphorylation deficiency 13 (MIM 614932). Despite phenotypic variability - common to disorders resulting from mitochondrial dysfunction - DD and ID of relevant severity to the current panel have been reported in several individuals published in the literature. Seizures may also be observed. Rius et al (2019 - PMID: 31752325) provide an overview of 24 affected individuals (7 new and 17 from previous studies). Neurodevelopmental features are summarized in fig.1 and additional details are provided in the supplement. Based on this review, seizures were present in 7 individuals (of the 18 for whom this information was available). PNPT1 encodes the mitochondrial polynucleotide phosphorylase, involved in the import of nuclear-encoded RNA to mitochondria. Loss of its activity has been shown to result in combined respiratory chain deficiency. However, as discussed by Rius et al and previous articles as well, OXPHOS studies in affected individuals may be normal or suggestive of only mild impairment due to tissue specificity and different assay methods used (eg. spectrophotometric vs dipstick activity assays). The same applies to lactate which was normal or mildly elevated in some affected individuals. Missense, pLoF function variants as well as a synonymous one leading to aberrant splicing (NM_033109.4:c.1818T>G) have been reported. Sources: Literature |
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| Intellectual disability v2.1129 | PNPT1 | Konstantinos Varvagiannis reviewed gene: PNPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31752325; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.356 | FBN1 | Rebecca Foulger Publications for gene: FBN1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.355 | FBN1 | Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from 'Both AD + AR' to 'MONOALLELIC' only to match current DDG2P Allelic requirement of 'monoallelic' for all confirmed disorders (SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME; MARFAN SYNDROME; MASS SYNDROME/OVERLAP CONNECTIVE TISSUE DISEASE). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.355 | FBN1 | Rebecca Foulger Mode of inheritance for gene: FBN1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.167 | FBN1 | Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from 'Both monoallelic and biallelic' to 'MONOALLELIC' to match current DDG2P Allelic requirement, which is 'monoallelic' for confirmed MARFAN SYNDROME, SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME, and MASS SYNDROME/OVERLAP CONNECTIVE TISSUE DISEASE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.167 | FBN1 | Rebecca Foulger Mode of inheritance for gene: FBN1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.166 | EMC1 | Rebecca Foulger Phenotypes for gene: EMC1 were changed from Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy. to Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy.; Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy, Biallelic; Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy, Monoallelic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.165 | EMC1 | Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from 'BOTH Monoallelic and biallelic' to just 'BIALLELIC' to match MOI of highest rated disorder (Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy, Biallelic). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.165 | EMC1 | Rebecca Foulger Mode of inheritance for gene: EMC1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.164 | EMC1 |
Rebecca Foulger commented on gene: EMC1: As of November 26th 2019, DDG2P ratings are: probable for Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy, Biallelic (biallelic, loss of function). possible for Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy, Monoallelic (monoallelic, dominant negative). possible for Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy (monoallelic, dominant negative. |
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| DDG2P v1.164 | CUL3 | Rebecca Foulger changed review comment from: Comment on list classification: Updated rating from Red to Green to match current probable rating in DDG2P for CUL3-related developmental disorder (monoallelic). Allelic requirement: monoallelic. Mutation consequence: loss of function.; to: Comment on list classification: Updated rating from Red to Amber to match current probable rating in DDG2P for CUL3-related developmental disorder (monoallelic). Allelic requirement: monoallelic. Mutation consequence: loss of function. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.164 | CUL3 | Rebecca Foulger Classified gene: CUL3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.164 | CUL3 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green to match current probable rating in DDG2P for CUL3-related developmental disorder (monoallelic). Allelic requirement: monoallelic. Mutation consequence: loss of function. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.164 | CUL3 | Rebecca Foulger Gene: cul3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.163 | CUL3 | Rebecca Foulger Phenotypes for gene: CUL3 were changed from CUL3 associated autism spectrum disorder to CUL3-related developmental disorder (monoallelic) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.162 | CRYBB1 |
Rebecca Foulger changed review comment from: As of November 26th 2019: DDG2P rating confirmed for CATARACT 17, MULTIPLE TYPES, MONOALLELIC (monoallelic, loss of function) DDG2P rating probable for CATARACT 17, MULTIPLE TYPES, BIALLELIC (biallelic, loss of function) DDG2P rating probable for CATARACT 17, MULTIPLE TYPES, BIALLELIC (biallelic, loss of function); to: As of November 26th 2019: DDG2P rating confirmed for CATARACT 17, MULTIPLE TYPES, MONOALLELIC (monoallelic, loss of function) DDG2P rating probable for CATARACT 17, MULTIPLE TYPES, BIALLELIC (biallelic, loss of function) DDG2P rating probable for CATARACT 17, MULTIPLE TYPES (biallelic, loss of function) |
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| DDG2P v1.162 | CRYBB1 | Rebecca Foulger Phenotypes for gene: CRYBB1 were changed from CATARACT 17, MULTIPLE TYPES; CATARACT 17, MULTIPLE TYPES, BIALLELIC to CATARACT 17, MULTIPLE TYPES, MONOALLELIC; CATARACT 17, MULTIPLE TYPES; CATARACT 17, MULTIPLE TYPES, BIALLELIC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.161 | CRYBB1 | Rebecca Foulger Phenotypes for gene: CRYBB1 were changed from CATARACT, CONGENITAL NUCLEAR, AUTOSOMAL RECESSIVE 3 611544 to CATARACT 17, MULTIPLE TYPES; CATARACT 17, MULTIPLE TYPES, BIALLELIC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.160 | CRYBB1 | Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from 'BOTH MONOALLELIC AND BIALLELIC' to 'MONOALLELIC only, to match MOI of confirmed disorder (CATARACT 17, MULTIPLE TYPES, MONOALLELIC). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.160 | CRYBB1 | Rebecca Foulger Mode of inheritance for gene: CRYBB1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.159 | CRYBB1 | Rebecca Foulger Tag watchlist tag was added to gene: CRYBB1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.159 | CRYBB1 | Rebecca Foulger commented on gene: CRYBB1: Added 'watchlist' tag to highlight different G2P ratings for different disorders. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.159 | CRYBB1 |
Rebecca Foulger commented on gene: CRYBB1: As of November 26th 2019: DDG2P rating confirmed for CATARACT 17, MULTIPLE TYPES, MONOALLELIC (monoallelic, loss of function) DDG2P rating probable for CATARACT 17, MULTIPLE TYPES, BIALLELIC (biallelic, loss of function) DDG2P rating probable for CATARACT 17, MULTIPLE TYPES, BIALLELIC (biallelic, loss of function) |
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| DDG2P v1.159 | COMP |
Rebecca Foulger commented on gene: COMP: As of November 26th 2019: DDG2P rating confirmed for PSEUDOACHONDROPLASIA (monoallelic, dominant negative). DDG2P rating possible for MULTIPLE EPIPHYSEAL DYSPLASIA TYPE 1 (monoallelic, dominant negative). Added 'watchlist' tag to highlight different G2P ratings for different disorders. |
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| DDG2P v1.159 | COMP | Rebecca Foulger changed review comment from: Original DDG2P rating: confirmed (for all listed disorders). DDG2P mode of pathogenicity for both disorers: dominant negative ; to: Original DDG2P rating: confirmed (for all listed disorders). DDG2P mode of pathogenicity for both disorders: dominant negative | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.159 | COMP | Rebecca Foulger Phenotypes for gene: COMP were changed from MULTIPLE EPIPHYSEAL DYSPLASIA TYPE 1 132400; ARE THE CAUSE OF PSEUDOACHONDROPLASIA 177170 to MULTIPLE EPIPHYSEAL DYSPLASIA TYPE 1 132400; PSEUDOACHONDROPLASIA, 177170 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.158 | COMP | Rebecca Foulger Tag watchlist tag was added to gene: COMP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.158 | CACNA1G | Rebecca Foulger commented on gene: CACNA1G: Added 'watchlist' tag to highlight different G2P ratings for different disorders. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.158 | CACNA1G | Rebecca Foulger Tag watchlist tag was added to gene: CACNA1G. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.158 | CACNA1G | Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from BIALLELIC to MONOALLELIC to reflect MOI of the disorder with the highest disease confidence (CACNA1G-related developmental disorder (monoallelic). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.158 | CACNA1G | Rebecca Foulger Mode of inheritance for gene: CACNA1G was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.157 | CACNA1G | Rebecca Foulger Classified gene: CACNA1G as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.157 | CACNA1G | Rebecca Foulger Added comment: Comment on list classification: Updated from Red to Amber for new disorder: CACNA1G-related developmental disorder (monoallelic). G2P Disease confidence: probable. G2P allelic requirement: monoallelic. G2P mutation consequence:loss of function. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.157 | CACNA1G | Rebecca Foulger Gene: cacna1g has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.156 | CACNA1G |
Rebecca Foulger changed review comment from: Original DDG2P rating: possible. ; to: Original DDG2P rating for AUTOSOMAL RECESSIVE MENTAL RETARDATION: possible. Allelic requirement: biallelic. Mutation consequence: loss of function. |
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| DDG2P v1.156 | CACNA1G | Rebecca Foulger Phenotypes for gene: CACNA1G were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to AUTOSOMAL RECESSIVE MENTAL RETARDATION; CACNA1G-related developmental disorder (monoallelic) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.155 | CACNA1E | Rebecca Foulger commented on gene: CACNA1E: Added 'watchlist' tag to highlight different G2P ratings for different disorders. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.155 | CACNA1E | Rebecca Foulger Tag watchlist tag was added to gene: CACNA1E. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.155 | ACTL6B | Rebecca Foulger Tag watchlist tag was added to gene: ACTL6B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.94 | MAGEL2 | Rebecca Foulger Phenotypes for gene: MAGEL2 were changed from Schaaf-Yang syndrome, 615547; ARTHROGRYPOSIS MULTIPLEX CONGENITA to Schaaf-Yang syndrome, 615547; ARTHROGRYPOSIS MULTIPLEX CONGENITA; Prader-Willi-Like syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.93 | MAGEL2 | Rebecca Foulger Publications for gene: MAGEL2 were set to 26365340; 27195816; 31504653; 29359444 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.92 | TTN | Rebecca Foulger Publications for gene: TTN were set to 24105469; 28040389; 31660661 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.91 | DPAGT1 | Rebecca Foulger Publications for gene: DPAGT1 were set to 26033833; 30653653; 22742743; 20301347 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.90 | SMN1 | Rebecca Foulger Phenotypes for gene: SMN1 were changed from arthrogryposis; SMA 0 to arthrogryposis; SMA 0; Spinal muscular atrophy-1, 253300; Spinal muscular atrophy-2, 253550; Spinal muscular atrophy-3, 253400; Spinal muscular atrophy-4, 271150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.89 | SMN1 | Rebecca Foulger Publications for gene: SMN1 were set to 27911332; 10700538; 11826188 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.88 | ATAD1 | Rebecca Foulger Classified gene: ATAD1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.88 | ATAD1 | Rebecca Foulger Added comment: Comment on list classification: Demoted ATAD1 from Green to Amber following review and advice from Zerin Hyder (Genomics England Clinical Team). The AMC phenotype is not yet well enough described for inclusion on the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.88 | ATAD1 | Rebecca Foulger Gene: atad1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.87 | GFM2 | Rebecca Foulger Classified gene: GFM2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.87 | GFM2 | Rebecca Foulger Added comment: Comment on list classification: Demoted GFM2 from Amber to Red following confirmation by Zerin Hyder (Genomics England Clinical Team): limited evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.87 | GFM2 | Rebecca Foulger Gene: gfm2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.86 | CACNA1E | Rebecca Foulger Classified gene: CACNA1E as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.86 | CACNA1E | Rebecca Foulger Added comment: Comment on list classification: Updated rating of CACNA1E from Amber to Green following review and confirmation from Zerin Hyder (Genomics England Clinical Team). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.86 | CACNA1E | Rebecca Foulger Gene: cacna1e has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.85 | CACNA1E | Rebecca Foulger Added comment: Comment on mode of pathogenicity: Set Mode of pathogenicity to 'Other' following Zerin Hyder's review about G.O.F variants in PMID:30343943 (Helbig et al., 2018). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.85 | CACNA1E | Rebecca Foulger Mode of pathogenicity for gene: CACNA1E was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1129 | PIK3C2A | Catherine Snow Classified gene: PIK3C2A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1129 | PIK3C2A | Catherine Snow Gene: pik3c2a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1128 | NTNG2 | Ellen McDonagh Classified gene: NTNG2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1128 | NTNG2 | Ellen McDonagh Added comment: Comment on list classification: Gene added by external reviewer and rated Green. 11 unrelated families reported with homozygous variants in this gene with a neurodevelopmental disorder including global developmental delay, plus functional evidence. Promoted to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1128 | NTNG2 | Ellen McDonagh Gene: ntng2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1128 | PIK3C2A |
Catherine Snow gene: PIK3C2A was added gene: PIK3C2A was added to Intellectual disability. Sources: Expert Review Mode of inheritance for gene: PIK3C2A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIK3C2A were set to 31034465 Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome, 618440 Review for gene: PIK3C2A was set to AMBER Added comment: PIK3C2A is on a number of panels including a Green rating on Skeletal dysplasia (Version 1.244) clinical support advised that as PIK3C2A phenotype includes DD, gene should be rated as Amber on this panel. Sources: Expert Review |
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| Intellectual disability v2.1127 | ZNF292 | Catherine Snow Deleted their review | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1127 | ZNF292 | Catherine Snow edited their review of gene: ZNF292: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1127 | ZNF292 | Catherine Snow reviewed gene: ZNF292: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1127 | FAM160B1 | Ellen McDonagh Classified gene: FAM160B1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1127 | FAM160B1 | Ellen McDonagh Added comment: Comment on list classification: Gene added by external reviewer, and promoted from grey to Red as the function of the protein/gene is still unknown at this stage. One family and another unrelated individual reported with developmental delay/ID and variants in this gene, however this will be kept red until further evidence arises. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1127 | FAM160B1 | Ellen McDonagh Gene: fam160b1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.84 | SMN1 | Zerin Hyder reviewed gene: SMN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10700538, 27911332, 8787675; Phenotypes: spinal muscular atrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.477 | SCAMP5 | Ellen McDonagh Added comment: Comment on mode of pathogenicity: A dominant negative effect is predicted. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.477 | SCAMP5 | Ellen McDonagh Mode of pathogenicity for gene: SCAMP5 was changed from Other to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1126 | SCAMP5 | Ellen McDonagh Classified gene: SCAMP5 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1126 | SCAMP5 | Ellen McDonagh Added comment: Comment on list classification: Gene added by external Reviewer, and promoted to Amber due to review and overall evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1126 | SCAMP5 | Ellen McDonagh Gene: scamp5 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.476 | SCAMP5 | Ellen McDonagh Classified gene: SCAMP5 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.476 | SCAMP5 | Ellen McDonagh Added comment: Comment on list classification: Gene added by external Reviewer, and promoted to Amber due to review and overall evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.476 | SCAMP5 | Ellen McDonagh Gene: scamp5 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1125 | ZNF292 | Ellen McDonagh Classified gene: ZNF292 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1125 | ZNF292 | Ellen McDonagh Added comment: Comment on list classification: Gene added by external reviewer. Promoted from grey to Amber due to the evidence presented, and reflecting the rating of 'probable' in Gene2Phenotype for ZNF292-related developmental disorder. At this stage, this has not been made Green due to uncertainty regarding the penetrance and the comment from the reviewer regarding manual review of some relevant LoF variants in gnomAD suggested that they represent false positive calls. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1125 | ZNF292 | Ellen McDonagh Gene: znf292 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.84 | CACNA1E | Zerin Hyder reviewed gene: CACNA1E: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30343943; Phenotypes: Epileptic encephalopathy, early infantile, 69; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult solid tumours cancer susceptibility v1.7 | RABL3 |
Israel Gomy gene: RABL3 was added gene: RABL3 was added to Adult solid tumours cancer susceptibility. Sources: Literature,Research Mode of inheritance for gene: RABL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RABL3 were set to 31406347 Phenotypes for gene: RABL3 were set to PANCREATIC CANCER, SUSCEPTIBILITY TO, 5; PNCA5 OMIM 618680 Penetrance for gene: RABL3 were set to unknown Mode of pathogenicity for gene: RABL3 was set to Other Review for gene: RABL3 was set to GREEN Added comment: Susceptibility to pancreatic ductal adenocarcinoma (PDAC) may be conferred by mutation in RABL3. Other cancers, including melanoma, breast cancer, and colon cancer, have been reported in RABL3 mutation-carrying individuals, with or without PDAC. Expression of S36X-mutant RABL3 in HEK293T cells resulted in enhanced cell proliferation consistent with an oncogenic effect. Zebrafish with truncated rabl3 protein developed cancers at a statistically significant elevated rate compared to wildtype sibs. Other studies in zebrafish confirmed the role of mutant RABL3 in promoting cancer susceptibility. Sources: Literature, Research |
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| Arthrogryposis v2.84 | ATAD1 | Zerin Hyder reviewed gene: ATAD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29659736, 29390050, 28180185; Phenotypes: Hyperekplexia 4; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.135 | TXNDC15 | Eleanor Williams Classified gene: TXNDC15 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.135 | TXNDC15 |
Eleanor Williams Added comment: Comment on list classification: Adding this gene to the panel as it is has been removed from the skeletal ciliopathies panel as the skeletal phenotype is polydactyly only. 3 cases reported with polydactyly as part of the phenotype. |
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| Limb disorders v1.135 | TXNDC15 | Eleanor Williams Gene: txndc15 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.134 | TXNDC15 |
Eleanor Williams gene: TXNDC15 was added gene: TXNDC15 was added to Limb disorders. Sources: Other Mode of inheritance for gene: TXNDC15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TXNDC15 were set to 27894351 Phenotypes for gene: TXNDC15 were set to Meckel-Gruber syndrome Review for gene: TXNDC15 was set to GREEN Added comment: Comment from copied from skeletal ciliopathies panel: Shaheen et al. 2016 (PMID:27894351) report TXNDC15 variants in two consanguineous Saudi families that share the features of Meckel-Gruber syndrome (a ciliopathy phenotype). Phenotypes of both patients included polydactyly; one patients was still born, and one survived till 11 hours old. Furthermore, through an international collaboration, they were able to identify an additional Meckel-Gruber syndrome patient (Pakistani origin) with a homozygous truncating variant in this gene. The patient also had polydactyly, although a sibling presented similarly but with no polydactyl. Patient fibroblasts had aberrant ciliogenesis. Sources: Other |
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| Limb disorders v1.133 | DDX59 | Eleanor Williams Classified gene: DDX59 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.133 | DDX59 | Eleanor Williams Added comment: Comment on list classification: Adding this gene back to the panel as it is has been removed from the skeletal ciliopathies panel as the skeletal phenotype is polydactyly only. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.133 | DDX59 | Eleanor Williams Gene: ddx59 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.132 | CENPF | Eleanor Williams Classified gene: CENPF as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.132 | CENPF | Eleanor Williams Added comment: Comment on list classification: Adding this gene to the panel as it is has been removed from the skeletal ciliopathies panel as the skeletal phenotype is polydactyly only. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.132 | CENPF | Eleanor Williams Gene: cenpf has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.131 | CENPF | Eleanor Williams Phenotypes for gene: CENPF were changed from Polydactyly to Polydactyly; Stromme syndrome 243605 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.130 | CENPF | Eleanor Williams Mode of inheritance for gene: CENPF was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.78 | ZNHIT3 | Louise Daugherty edited their review of gene: ZNHIT3: Added comment: Gene rated Red- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.78 | UFC1 | Louise Daugherty Classified gene: UFC1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.78 | UFC1 | Louise Daugherty Added comment: Comment on list classification: Gene rated Green- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.78 | UFC1 | Louise Daugherty Gene: ufc1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.77 | UFM1 | Louise Daugherty commented on gene: UFM1: Gene rated Green this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.77 | UBA5 | Louise Daugherty Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.77 | UBA5 | Louise Daugherty Classified gene: UBA5 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.77 | UBA5 | Louise Daugherty Added comment: Comment on list classification: Gene rated Green- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.77 | UBA5 | Louise Daugherty Gene: uba5 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.76 | UBA5 | Louise Daugherty changed review comment from: Gene rated Red- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature; to: Gene rated Green- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.76 | UBA5 | Louise Daugherty edited their review of gene: UBA5: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.76 | UBA5 | Louise Daugherty edited their review of gene: UBA5: Added comment: Gene rated Red- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.21 | SUFU | Eleanor Williams changed review comment from: PMID:28965847 - De Mori et al 2017 - All subjects presented peculiar facial dysmorphisms (hypertelorism, broad and depressed nasal bridge, frontal bossing), oculomotor apraxia, developmental delay with mild intellectual impairment, gait ataxia, and dysarthria. Three of them had post-axial polydactyly and two had global macrosomia with macrocephaly. One child also showed a few small dyskeratotic pits on the foot soles; to: PMID:28965847 - De Mori et al 2017 - 4 subjects from 2 families. All subjects presented peculiar facial dysmorphisms (hypertelorism, broad and depressed nasal bridge, frontal bossing), oculomotor apraxia, developmental delay with mild intellectual impairment, gait ataxia, and dysarthria. Three of them had post-axial polydactyly and two had global macrosomia with macrocephaly. One child also showed a few small dyskeratotic pits on the foot soles | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.76 | CCDC88A | Louise Daugherty edited their review of gene: CCDC88A: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.76 | PCLO | Louise Daugherty edited their review of gene: PCLO: Added comment: Gene rated Red- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.76 | CCDC88A | Louise Daugherty Publications for gene: CCDC88A were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.75 | CCDC88A | Louise Daugherty Classified gene: CCDC88A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.75 | CCDC88A | Louise Daugherty Added comment: Comment on list classification: Gene rated Amber- this rating was suggested in an email to the test group on 6th November after review by Genomics England clinical team review, and indicating if there were no further comments on the rating the gene would rated as per provisional suggestion as per recommended on the current evidence in the literature | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe microcephaly v1.75 | CCDC88A | Louise Daugherty Gene: ccdc88a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.129 | WDPCP |
Eleanor Williams commented on gene: WDPCP: PMID: 28289185 - Bruel et al 2017 - report 1 case (patient 10) with compound heterozygous variants in WDPCP and an Oral-facial-digital syndrome phenotype which includes Post-axial polydactyly of the hands and syndactyly of the feet. PMID: 27158779 - Toriyama et al 2016 - report 1 case of a 5-year-old male presenting with facial dysmorphism, tongue hamartoma, high arched palate, tooth abnormalities, and postaxial polydactyly. He was found to be compound heterozygous for two mutations in WDPCP, a frameshift and a missense variant predicted to alter splicing. Each parent had one of the variants. Functional studies in Xenopus MCCs and found that the frame-shift allele resulted in total loss of protein, while the point mutation led to a consistent but more modest defect in protein stability They also observed Y-shaped metacarpals and defects in tongue and palate morphology in Wdpcp mouse mutants PMID: 25427950 - Saari et al 2015 - report 1 case of a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas. By whole exome sequencing they found she is a compound heterozygote for a frame shift mutation and a likely pathogenic sequence variant in WDPCP. The parents and two siblings were heterozygous carriers. PMID: Kim et al 2010 - report 1 cases of a proband with a clinical diagnosis of BBS and a homozygous Fritz mutation that segregated with the disorder. Both parents and an unaffected sib were heterozygous carriers. No details 3 cases with oralfacial digitial syndrome type phenotypes and one with a clinical diagnosis of BBS. |
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| Skeletal ciliopathies v0.21 | WDPCP |
Eleanor Williams changed review comment from: PMID: 28289185 - Bruel et al 2017 - report 1 case (patient 10) with compound heterozygous variants in WDPCP and an Oral-facial-digital syndrome phenotype which includes Post-axial polydactyly of the hands and syndactyly of the feet. PMID: 27158779 - Toriyama et al 2016 - report 1 case of a 5-year-old male presenting with facial dysmorphism, tongue hamartoma, high arched palate, tooth abnormalities, and postaxial polydactyly. He was found to be compound heterozygous for two mutations in WDPCP, a frameshift and a missense variant predicted to alter splicing. Each parent had one of the variants. Functional studies in Xenopus MCCs and found that the frame-shift allele resulted in total loss of protein, while the point mutation led to a consistent but more modest defect in protein stability They also observed Y-shaped metacarpals and defects in tongue and palate morphology in Wdpcp mouse mutants PMID: 25427950 - Saari et al 2015 - report 1 case of a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas. By whole exome sequencing they found she is a compound heterozygote for a frame shift mutation and a likely pathogenic sequence variant in WDPCP. The parents and two siblings were heterozygous carriers. PMID: Kim et al 2010 - report 1 cases of a proband with a clinical diagnosis of BBS and a homozygous Fritz mutation that segregated with the disorder. Both parents and an unaffected sib were heterozygous carriers. No details 3 cases with orofacial digitial syndrome type phenotypes and one with a clinical diagnosis of BBS.; to: PMID: 28289185 - Bruel et al 2017 - report 1 case (patient 10) with compound heterozygous variants in WDPCP and an Oral-facial-digital syndrome phenotype which includes Post-axial polydactyly of the hands and syndactyly of the feet. PMID: 27158779 - Toriyama et al 2016 - report 1 case of a 5-year-old male presenting with facial dysmorphism, tongue hamartoma, high arched palate, tooth abnormalities, and postaxial polydactyly. He was found to be compound heterozygous for two mutations in WDPCP, a frameshift and a missense variant predicted to alter splicing. Each parent had one of the variants. Functional studies in Xenopus MCCs and found that the frame-shift allele resulted in total loss of protein, while the point mutation led to a consistent but more modest defect in protein stability They also observed Y-shaped metacarpals and defects in tongue and palate morphology in Wdpcp mouse mutants PMID: 25427950 - Saari et al 2015 - report 1 case of a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas. By whole exome sequencing they found she is a compound heterozygote for a frame shift mutation and a likely pathogenic sequence variant in WDPCP. The parents and two siblings were heterozygous carriers. PMID: Kim et al 2010 - report 1 cases of a proband with a clinical diagnosis of BBS and a homozygous Fritz mutation that segregated with the disorder. Both parents and an unaffected sib were heterozygous carriers. No details 3 cases with oralfacial digitial syndrome type phenotypes and one with a clinical diagnosis of BBS. |
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| Skeletal ciliopathies v0.21 | WDPCP |
Eleanor Williams commented on gene: WDPCP: PMID: 28289185 - Bruel et al 2017 - report 1 case (patient 10) with compound heterozygous variants in WDPCP and an Oral-facial-digital syndrome phenotype which includes Post-axial polydactyly of the hands and syndactyly of the feet. PMID: 27158779 - Toriyama et al 2016 - report 1 case of a 5-year-old male presenting with facial dysmorphism, tongue hamartoma, high arched palate, tooth abnormalities, and postaxial polydactyly. He was found to be compound heterozygous for two mutations in WDPCP, a frameshift and a missense variant predicted to alter splicing. Each parent had one of the variants. Functional studies in Xenopus MCCs and found that the frame-shift allele resulted in total loss of protein, while the point mutation led to a consistent but more modest defect in protein stability They also observed Y-shaped metacarpals and defects in tongue and palate morphology in Wdpcp mouse mutants PMID: 25427950 - Saari et al 2015 - report 1 case of a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas. By whole exome sequencing they found she is a compound heterozygote for a frame shift mutation and a likely pathogenic sequence variant in WDPCP. The parents and two siblings were heterozygous carriers. PMID: Kim et al 2010 - report 1 cases of a proband with a clinical diagnosis of BBS and a homozygous Fritz mutation that segregated with the disorder. Both parents and an unaffected sib were heterozygous carriers. No details 3 cases with orofacial digitial syndrome type phenotypes and one with a clinical diagnosis of BBS. |
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| Intellectual disability v2.1124 | AP1B1 | Catherine Snow Classified gene: AP1B1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1124 | AP1B1 | Catherine Snow Gene: ap1b1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1123 | AP1B1 | Catherine Snow reviewed gene: AP1B1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.84 | DHCR24 | Zerin Hyder changed review comment from: Schaaf et al: one case with dermosterolsis with relative macrocephaly, mild arthrogryposis, and dysmorphic facial features. The diagnosis of desmosterolosis was established by detection of significant elevation of plasma desmosterol levels and reduced enzyme activity of DHCR24 upon expression of the patient's DHCR24 cDNA. The patient was found to be a compound heterozygote for c.281G>A (p.R94H) and c.1438G>A (p.E480K) mutations. 4 individuals in Bedouin kindred with dermosterolsis and distal contractures. Two other reports 12457401; 29175559 in association with milder phenotype of AMC.; to: Schaaf et al: patient with dermosterolsis with relative macrocephaly, mild arthrogryposis, and dysmorphic facial features. The diagnosis of desmosterolosis was established by detection of significant elevation of plasma desmosterol levels and reduced enzyme activity of DHCR24 upon expression of the patient's DHCR24 cDNA. The patient was found to be a compound heterozygote for c.281G>A (p.R94H) and c.1438G>A (p.E480K) mutations. 4 individuals in Bedouin kindred with dermosterolsis and distal contractures. Two other reports 12457401; 29175559 in association with milder phenotype of AMC. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.84 | DHCR24 | Zerin Hyder reviewed gene: DHCR24: Rating: GREEN; Mode of pathogenicity: None; Publications: 21671375, 12457401, 29175559, 21559050; Phenotypes: Desmosterolosis 602398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.84 | ALG3 | Zerin Hyder reviewed gene: ALG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16006436, 26453362, 28742265; Phenotypes: Congenital disorder of glycosylation, type Id 601110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.25 | SLC4A3 | Ivone Leong Classified gene: SLC4A3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.25 | SLC4A3 | Ivone Leong Added comment: Comment on list classification: Demoted from Green to Amber based on the previously submitted review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.25 | SLC4A3 | Ivone Leong Gene: slc4a3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.135 | TTC25 | Louise Daugherty Classified gene: TTC25 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.135 | TTC25 | Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Amber after expert review. Change of rating will be included in update with Test Group to enable further comment/review if required before sign off. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.135 | TTC25 | Louise Daugherty Gene: ttc25 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.134 | DNAL1 | Louise Daugherty Classified gene: DNAL1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.134 | DNAL1 | Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Amber after expert review. Change of rating will be included in update with Test Group to enable further comment/review if required before sign off. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.134 | DNAL1 | Louise Daugherty Gene: dnal1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.24 | SLC22A5 | Ivone Leong Classified gene: SLC22A5 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.24 | SLC22A5 | Ivone Leong Added comment: Comment on list classification: Demoted from Green to Red as the GMS Cardiology specialist group feels that this gene should not be on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.24 | SLC22A5 | Ivone Leong Gene: slc22a5 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.133 | DNAAF2 | Louise Daugherty Classified gene: DNAAF2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.133 | DNAAF2 | Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Amber after expert review. Change of rating will be included in update with Test Group to enable further comment/review if required before sign off. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.133 | DNAAF2 | Louise Daugherty Gene: dnaaf2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.132 | CFC1 | Louise Daugherty Classified gene: CFC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.132 | CFC1 | Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Amber after expert review. Change of rating will be included in update with Test Group to enable further comment/review if required before sign off. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.132 | CFC1 | Louise Daugherty Gene: cfc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.84 | DPAGT1 |
Zerin Hyder changed review comment from: Green gene on neuromuscular arthrogryposis panel. Ganetzky et al, 2015: Newborn female with arthrogryposis multiplex due to fetal akinesia. Transferrin isoelectric focusing was suggestive of a type I congenital disorder of glycosylation; sequencing revealed homozygous missense mutation in DPAGT1. Carrera et al: DPAGT1-CDG in patient with fetal hypokinesia and AMC. Contractures reported in association with congenital myaesthenic syndrome in 23447650; to: Green gene on neuromuscular arthrogryposis panel. Ganetzky et al, 2015: Newborn female with arthrogryposis multiplex due to fetal akinesia. Transferrin isoelectric focusing was suggestive of a type I congenital disorder of glycosylation; sequencing revealed homozygous missense mutation in DPAGT1. Carrera et al: DPAGT1-CDG in patient with fetal hypokinesia and AMC. Multiple joint contractures reported in association with congenital myaesthenic syndrome and DPAGT1 mutations. |
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| Arthrogryposis v2.84 | DPAGT1 |
Zerin Hyder changed review comment from: Green gene on neuromuscular arthrogryposis panel. Ganetzky et al, 2015: Newborn female with arthrogryposis multiplex due to fetal akinesia. Transferrin isoelectric focusing was suggestive of a type I congenital disorder of glycosylation; sequencing revealed homozygous missense mutation in DPAGT1. Carrera et al: DPAGT1-CDG in patient with fetal hypokinesia and AMC. Contractures reported in association with congenital myaesthenic syndrome.; to: Green gene on neuromuscular arthrogryposis panel. Ganetzky et al, 2015: Newborn female with arthrogryposis multiplex due to fetal akinesia. Transferrin isoelectric focusing was suggestive of a type I congenital disorder of glycosylation; sequencing revealed homozygous missense mutation in DPAGT1. Carrera et al: DPAGT1-CDG in patient with fetal hypokinesia and AMC. Contractures reported in association with congenital myaesthenic syndrome in 23447650 |
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| Arthrogryposis v2.84 | DPAGT1 | Zerin Hyder reviewed gene: DPAGT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26033833, 22786653, 30653653, 22492991; Phenotypes: Congenital disorder of glycosylation, type Ij; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.84 | TTN | Zerin Hyder reviewed gene: TTN: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 24105469, 31660661, 29575618, 28040389; Phenotypes: Salih myopathy, Muscular dystrophy, limb-girdle, autosomal recessive 10; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.131 | ACVR2B | Louise Daugherty changed review comment from: Comment on list classification: Downgraded from Green to Red after expert review. Included update to Test Group to comment on this change before sign off.; to: Comment on list classification: Downgraded from Green to Red after expert review. Change of rating will be included in update with Test Group to enable further comment/review if required before sign off. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.131 | ACVR2B | Louise Daugherty Classified gene: ACVR2B as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.131 | ACVR2B | Louise Daugherty Added comment: Comment on list classification: Downgraded from Green to Red after expert review. Included update to Test Group to comment on this change before sign off. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.131 | ACVR2B | Louise Daugherty Gene: acvr2b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.84 | MAGEL2 | Zerin Hyder reviewed gene: MAGEL2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24076603, 27195816, 26365340; Phenotypes: Schaaf-Yang syndrome, Prader-Willi-Like syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.23 | SLC22A5 | Juan Pablo Kaski reviewed gene: SLC22A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 26190315, 29198778, 31472821; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.130 | NME8 | Louise Daugherty Mode of inheritance for gene: NME8 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.129 | NME8 | Louise Daugherty Publications for gene: NME8 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.128 | GDF1 | Louise Daugherty Mode of inheritance for gene: GDF1 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.127 | ZMYND10 | Louise Daugherty Phenotypes for gene: ZMYND10 were changed from Congenital heart defects, nonsyndromic, 1, X-linked; Heterotaxy, visceral, 1, X-linked; VACTERL association, X-linked to Ciliary dyskinesia, primary, 22, 615444 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.126 | ZMYND10 | Louise Daugherty Mode of inheritance for gene: ZMYND10 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.125 | ZMYND10 | Louise Daugherty Phenotypes for gene: ZMYND10 were changed from to Congenital heart defects, nonsyndromic, 1, X-linked; Heterotaxy, visceral, 1, X-linked; VACTERL association, X-linked | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.124 | ZMYND10 | Louise Daugherty Mode of inheritance for gene: ZMYND10 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.123 | ZIC3 | Louise Daugherty Phenotypes for gene: ZIC3 were changed from to Heterotaxy, visceral, 1, X-linked, 306955; Congenital heart defects, nonsyndromic, 1, X-linked | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.122 | ZIC3 | Louise Daugherty Mode of inheritance for gene: ZIC3 was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.121 | TTC25 | Louise Daugherty Phenotypes for gene: TTC25 were changed from to Ciliary dyskinesia, primary, 35, 617092 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.120 | TTC25 | Louise Daugherty Publications for gene: TTC25 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.119 | TTC25 | Louise Daugherty Mode of inheritance for gene: TTC25 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.118 | SPAG1 | Louise Daugherty Phenotypes for gene: SPAG1 were changed from to Ciliary dyskinesia, primary, 28, 615505 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.117 | SPAG1 | Louise Daugherty Publications for gene: SPAG1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.116 | SPAG1 | Louise Daugherty Mode of inheritance for gene: SPAG1 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.115 | PIH1D3 | Louise Daugherty Phenotypes for gene: PIH1D3 were changed from to Ciliary dyskinesia, primary, 36, X-linked, 300991 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.114 | PIH1D3 | Louise Daugherty Publications for gene: PIH1D3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.113 | PIH1D3 | Louise Daugherty Mode of inheritance for gene: PIH1D3 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.112 | NODAL | Louise Daugherty Phenotypes for gene: NODAL were changed from Heterotaxy, visceral, 5270100 to Heterotaxy, visceral, 5, 270100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.111 | NODAL | Louise Daugherty Phenotypes for gene: NODAL were changed from to Heterotaxy, visceral, 5270100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.110 | NODAL | Louise Daugherty Mode of inheritance for gene: NODAL was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.109 | MMP21 | Louise Daugherty Phenotypes for gene: MMP21 were changed from to Heterotaxy, visceral, 7, autosomal, 616749 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.108 | MMP21 | Louise Daugherty Publications for gene: MMP21 were set to 26437028 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.107 | MMP21 | Louise Daugherty Mode of inheritance for gene: MMP21 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.106 | LRRC6 | Louise Daugherty Phenotypes for gene: LRRC6 were changed from to Ciliary dyskinesia, primary, 19, 614935 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.105 | LRRC6 | Louise Daugherty Publications for gene: LRRC6 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.104 | LRRC6 | Louise Daugherty Mode of inheritance for gene: LRRC6 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.103 | LRRC56 | Louise Daugherty Phenotypes for gene: LRRC56 were changed from Ciliary dyskinesia, primary, 39, 618254; Mucociliary Clearance and Laterality Defe to Ciliary dyskinesia, primary, 39, 618254; Mucociliary Clearance and Laterality Defect | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.102 | GDF1 | Louise Daugherty Phenotypes for gene: GDF1 were changed from to Right atrial isomerism, 208530 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.101 | GDF1 | Louise Daugherty Publications for gene: GDF1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.100 | DNAL1 | Louise Daugherty Publications for gene: DNAL1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.99 | DNAL1 | Louise Daugherty Phenotypes for gene: DNAL1 were changed from to Ciliary dyskinesia, primary, 16, 614017 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.98 | DNAL1 | Louise Daugherty Mode of inheritance for gene: DNAL1 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.97 | DNAI2 | Louise Daugherty Phenotypes for gene: DNAI2 were changed from to Ciliary dyskinesia, primary, 9, with or without situs inversus, 612444 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.96 | DNAI2 | Louise Daugherty Publications for gene: DNAI2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.95 | DNAI2 | Louise Daugherty Mode of inheritance for gene: DNAI2 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.94 | DNAI1 | Louise Daugherty Phenotypes for gene: DNAI1 were changed from to Ciliary dyskinesia, primary, 1, with or without situs inversus, 244400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.93 | DNAI1 | Louise Daugherty Publications for gene: DNAI1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.92 | DNAI1 | Louise Daugherty Mode of inheritance for gene: DNAI1 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.91 | DNAH9 | Louise Daugherty Phenotypes for gene: DNAH9 were changed from Primary ciliary dyskinesia to Primary ciliary dyskinesia, 40, 618300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.90 | DNAH9 | Louise Daugherty Publications for gene: DNAH9 were set to 30471717 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.89 | DNAH5 | Louise Daugherty Phenotypes for gene: DNAH5 were changed from to Ciliary dyskinesia, primary, 3, with or without situs inversus, 608644 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.88 | DNAH5 | Louise Daugherty Publications for gene: DNAH5 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.87 | DNAH5 | Louise Daugherty Mode of inheritance for gene: DNAH5 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.86 | DNAH11 | Louise Daugherty Phenotypes for gene: DNAH11 were changed from to Ciliary dyskinesia, primary, 7, with or without situs inversus, 611884 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.85 | DNAH11 | Louise Daugherty Publications for gene: DNAH11 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.84 | DNAH11 | Louise Daugherty Mode of inheritance for gene: DNAH11 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.83 | DNAAF5 | Louise Daugherty Phenotypes for gene: DNAAF5 were changed from to Ciliary dyskinesia, primary, 18, 614874 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.82 | DNAAF5 | Louise Daugherty Publications for gene: DNAAF5 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.81 | DNAAF5 | Louise Daugherty Mode of inheritance for gene: DNAAF5 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.80 | DNAAF4 | Louise Daugherty Phenotypes for gene: DNAAF4 were changed from to Ciliary dyskinesia, primary, 25, 615482 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.79 | DNAAF4 | Louise Daugherty Publications for gene: DNAAF4 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.78 | DNAAF4 | Louise Daugherty Mode of inheritance for gene: DNAAF4 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.77 | DNAAF3 | Louise Daugherty Phenotypes for gene: DNAAF3 were changed from to Ciliary dyskinesia, primary, 2, 606763 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1123 | FDFT1 | Catherine Snow Classified gene: FDFT1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1123 | FDFT1 | Catherine Snow Gene: fdft1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.76 | DNAAF3 | Louise Daugherty Mode of inheritance for gene: DNAAF3 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.75 | DNAAF3 | Louise Daugherty Publications for gene: DNAAF3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1122 | FDFT1 | Catherine Snow reviewed gene: FDFT1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.74 | DNAAF2 | Louise Daugherty Phenotypes for gene: DNAAF2 were changed from to Ciliary dyskinesia, primary, 10, 612518 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.73 | DNAAF2 | Louise Daugherty Mode of inheritance for gene: DNAAF2 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.72 | DNAAF2 | Louise Daugherty Publications for gene: DNAAF2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.71 | DNAAF1 | Louise Daugherty Phenotypes for gene: DNAAF1 were changed from to Ciliary dyskinesia, primary, 13, 613193 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.70 | DNAAF1 | Louise Daugherty Publications for gene: DNAAF1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.69 | DNAAF1 | Louise Daugherty Mode of inheritance for gene: DNAAF1 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.68 | CFC1 | Louise Daugherty Mode of inheritance for gene: CFC1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.67 | CFC1 | Louise Daugherty Phenotypes for gene: CFC1 were changed from to Heterotaxy, visceral, 2, 605376 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.66 | CFC1 | Louise Daugherty Publications for gene: CFC1 were set to 11062482 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.65 | CFAP53 | Louise Daugherty Phenotypes for gene: CFAP53 were changed from to Heterotaxy, visceral, 6, autosomal recessive, 614779 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.64 | CFAP53 | Louise Daugherty Publications for gene: CFAP53 were set to 26531781; 22577226; 25504577 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.63 | CFAP53 | Louise Daugherty Mode of inheritance for gene: CFAP53 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.62 | CCDC40 | Louise Daugherty Publications for gene: CCDC40 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.61 | CCDC40 | Louise Daugherty Phenotypes for gene: CCDC40 were changed from to Ciliary dyskinesia, primary, 15, 613808 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.60 | CCDC40 | Louise Daugherty Mode of inheritance for gene: CCDC40 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.59 | CCDC39 | Louise Daugherty Phenotypes for gene: CCDC39 were changed from to Ciliary dyskinesia, primary, 14, 613807 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.58 | CCDC39 | Louise Daugherty Publications for gene: CCDC39 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.57 | CCDC39 | Louise Daugherty Mode of inheritance for gene: CCDC39 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.56 | CCDC151 | Louise Daugherty Publications for gene: CCDC151 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.55 | CCDC114 | Louise Daugherty Publications for gene: CCDC114 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.54 | CCDC103 | Louise Daugherty Publications for gene: CCDC103 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.53 | C11orf70 | Louise Daugherty Publications for gene: C11orf70 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.52 | ARMC4 | Louise Daugherty Publications for gene: ARMC4 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.475 | TMX2 |
Konstantinos Varvagiannis gene: TMX2 was added gene: TMX2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: TMX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMX2 were set to 31586943; 31735293; 31270415 Phenotypes for gene: TMX2 were set to Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormal cortical gyration Penetrance for gene: TMX2 were set to Complete Review for gene: TMX2 was set to GREEN Added comment: This gene was reviewed for the intellectual disability panel. Epilepsy is part of the phenotype. Therefore green rating should be considered. From the ID panel : A recent report by Vandervore, Schot et al. following the previous review (Am J Hum Genet. 2019 Nov 12 - PMID: 31735293), provides further evidence that biallelic TMX2 mutations cause malformations of cortical development, microcephaly, DD and ID and epilepsy. As a result this gene should probably be considered for inclusion in the ID/epilepsy panels with green rating. Overall, 14 affected subjects from 10 unrelated families are reported in the aforementioned study. The majority had severe DD/ID (failure to achieve milestones, absent speech/ambulation and signs of cerebral palsy) with few having a somewhat milder impairment. 12 (of the 14) presented with epilepsy (spasms, myoclonic seizures, focal seizures with/without generalization or generalized tonic-clonic seizures) with onset most often in early infancy. Upon brain MRI (in 12 individuals), 5 presented polymicrogyria, 2 others pachygyria, 4 with brain atrophy, etc. All individuals were found to harbor biallelic TMX2 mutations by exome sequencing while previous investigations in several had ruled out alternative causes (infections, metabolic or chromosomal anomalies). Missense variants, an in-frame deletion as well as pLoF (stopgain/frameshift) variants were reported. [NM_015959.3 used as ref below]. The effect of variants was supported by mRNA studies, eg. RT-qPCR/allele specific RT-qPCR. The latter proved reduced expression for a frameshift variant (c.391dup / p.Leu131Profs*6) most likely due to NMD. Total mRNA levels were also 23% lower in an individual compound htz for a missense variant and a stopgain one localized in the last exon (c.757C>T / p.Arg253*). As for the previously reported c.614G>A (p.Arg205Gln), affecting the last nucleotide of exon 6, total mRNA in skin fibroblasts from a homozygous individual was not significantly decreased. RNA-Seq however demonstrated the presence of 4 different transcripts (roughly 25% each), one representing the regular mRNA, one with intron 6 retention (also present at low levels in healthy individuals), one with loss of 11 nucleotides within exon 6 and a fourth one due to in-frame skipping of exon 6. *To the best of my understanding : Thioredoxin (TRX)-related transmembrane proteins (TMX) belong to the broader family of oxidoreductases of protein disulfide isomerase (PDI) having an important role in protein folding. Study of the data from the Allen Human Brain Atlas suggest relevant fetal expression also increasing during postnatal life. As RNA-seq was carried out for 2 individuals, GO analysis suggested that the most deregulated clusters of genes are implicated in post-translational protein modifications (as would be expected for PDIs), membranes and synapse while pathway analysis suggested that relevant categories were inhibited eg. nervous system development/function and cell growth/proliferation/survival. Upon transfection of HEK293T cells, exogenous TMX2 was shown to co-localize with calnexin (CNX) to the (ER) mitochondria-associated-membrane. Mass-spectrometry based analysis of co-immunoprecipitated proteins confirmed interaction with CNX but also other regulators of calcium homeostasis, mitochondrial membrane components and respiratory chain NADH dehydrogenase. Study of the mitochondrial activity of TMX2-deficient fibroblasts suggested reduced respiratory reserve capacity, compensated by increased glycolytic activity. TMX2 occurs in both reduced and oxidized monomeric form. It also forms (homo)dimers with the ratio of dimers/monomers increasing under conditions of oxidative stress. Variant TMX2 increased propensity to form dimers, thus mimicking increased oxidative state. This was observed under stress but also under native conditions. --------- Created: 26 Nov 2019, 11:21 p.m. | Last Modified: 26 Nov 2019, 11:21 p.m. Panel Version: 2.1122 [Previous review] PMID: 31586943 - Ghosh et al. 2019 - reported on 8 individuals from 4 consanguineous families from the Middle East and Central Asia, all with a phenotype of DD/ID, seizures and microcephaly with lissencephaly (microlissencephaly is the term applying to the combination of two) upon brain MRI. All patients were investigated by exome sequencing and the variant localized within a region of ROH which was common to all 4 families. All were homozygous for a TMX2 missense variant (NM_001144012.2:c.500G>A or p.Arg167Gln / NM_015959.4:c.614G>A p.Arg205Gln or hg38 - Chr11:g.57739039G>A). The variant was considered to be the best candidate, upon review of all other homozygous ones. Sanger sequencing confirmed homozygosity for the variant in affected subjects, with additional compatible segregation studies including parents in all families as well as unaffected sibs (in two families). Despite presence of the same mutation in all, several proximal to this variant SNPs did not appear to be shared among the families studied, thus suggesting that the variant had arisen within different haplotype blocks. The authors comment that the variant was not previously identified in public databases. (The variant seems to correspond to rs370455806, present in 10 htz individuals in gnomAD, as well as in the GME database [GME Genotype Count 992:0:1 (hmz?) | Allele Count: 2,1984] . GME includes primarily - although not necessarily - healthy individuals). This SNV affecting the last nucleotide of an exon of several transcripts (correct ref. is NM_001144012.2 as appears in the supplement / using NM_001347898.1 as in the fig./text the variant would lie within an intron), an eventual splicing effect was studied. mRNA transcript levels were assessed following RT-PCR using different sets of primers. There was no evidence of novel splice isoforms but mRNA levels were reduced compared to controls (15-50% in affected individuals, to a lesser level in carriers). This led to the hypothesis that NMD of an aberrantly spliced mRNA might apply, although this was not proven. TMX2 encodes a protein disulfide isomerase (PDI). PDIs are transmembrane ER proteins which have a critical role in protein folding (PMID cited: 12670024). There were no relevant studies carried out in the article. As for animal models, the authors comment that mice homozygous for null mutations display preweaning lethality with complete penetrance.(http://www.informatics.jax.org/diseasePortal/popup?isPhenotype=true&markerID=MGI:1914208&header=mortality/aging). ------- Previously, Schot el al. (ESHG Conference 2018 Oral Presentation - Mutations in the thioredoxin related gene TMX2 cause primary microcephaly, polymicrogyria and severe neurodegeneration with impaired mitochondrial energy metabolism - available in PMID: 31270415 / https://www.nature.com/articles/s41431-019-0407-4 ) reported on 7 individuals from 5 unrelated families with biallelic TMX2 mutations. A newborn with microcephaly, polymicrogyria who died of refractory epilepsy, was compound heterozygous for 2 TMX2 variants. 6 additional individuals (from 4 unrelated families) with similar phenotype were found to harbor biallelic TMX2 mutations. It was commented that TMX2 is enriched in mitochondria-associated membrane of the ER with a role in ER stress protection and regulation of neuronal apoptosis. In line with this, fibroblasts from 2 unrelated patients showed secondary OXPHOS deficiency and increased glycolytic activity (the latter possibly as a compensatory mechanism). ------- There is no associated phenotype in OMIM/G2P/SysID. ------- Overall this gene could be considered for inclusion in the ID/epilepsy panel probably with amber (/red) rating pending further evidence. Sources: Literature Sources: Literature |
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| Intellectual disability v2.1122 | TMX2 | Konstantinos Varvagiannis edited their review of gene: TMX2: Changed publications: 31586943, 31270415, 31735293 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1122 | TMX2 |
Konstantinos Varvagiannis edited their review of gene: TMX2: Added comment: A recent report by Vandervore, Schot et al. following the previous review (Am J Hum Genet. 2019 Nov 12 - PMID: 31735293), provides further evidence that biallelic TMX2 mutations cause malformations of cortical development, microcephaly, DD and ID and epilepsy. As a result this gene should probably be considered for inclusion in the ID/epilepsy panels with green rating. Overall, 14 affected subjects from 10 unrelated families are reported in the aforementioned study. The majority had severe DD/ID (failure to achieve milestones, absent speech/ambulation and signs of cerebral palsy) with few having a somewhat milder impairment. 12 (of the 14) presented with epilepsy (spasms, myoclonic seizures, focal seizures with/without generalization or generalized tonic-clonic seizures) with onset most often in early infancy. Upon brain MRI (in 12 individuals), 5 presented polymicrogyria, 2 others pachygyria, 4 with brain atrophy, etc. All individuals were found to harbor biallelic TMX2 mutations by exome sequencing while previous investigations in several had ruled out alternative causes (infections, metabolic or chromosomal anomalies). Missense variants, an in-frame deletion as well as pLoF (stopgain/frameshift) variants were reported. [NM_015959.3 used as ref below]. The effect of variants was supported by mRNA studies, eg. RT-qPCR/allele specific RT-qPCR. The latter proved reduced expression for a frameshift variant (c.391dup / p.Leu131Profs*6) most likely due to NMD. Total mRNA levels were also 23% lower in an individual compound htz for a missense variant and a stopgain one localized in the last exon (c.757C>T / p.Arg253*). As for the previously reported c.614G>A (p.Arg205Gln), affecting the last nucleotide of exon 6, total mRNA in skin fibroblasts from a homozygous individual was not significantly decreased. RNA-Seq however demonstrated the presence of 4 different transcripts (roughly 25% each), one representing the regular mRNA, one with intron 6 retention (also present at low levels in healthy individuals), one with loss of 11 nucleotides within exon 6 and a fourth one due to in-frame skipping of exon 6. *To the best of my understanding : Thioredoxin (TRX)-related transmembrane proteins (TMX) belong to the broader family of oxidoreductases of protein disulfide isomerase (PDI) having an important role in protein folding. Study of the data from the Allen Human Brain Atlas suggest relevant fetal expression also increasing during postnatal life. As RNA-seq was carried out for 2 individuals, GO analysis suggested that the most deregulated clusters of genes are implicated in post-translational protein modifications (as would be expected for PDIs), membranes and synapse while pathway analysis suggested that relevant categories were inhibited eg. nervous system development/function and cell growth/proliferation/survival. Upon transfection of HEK293T cells, exogenous TMX2 was shown to co-localize with calnexin (CNX) to the (ER) mitochondria-associated-membrane. Mass-spectrometry based analysis of co-immunoprecipitated proteins confirmed interaction with CNX but also other regulators of calcium homeostasis, mitochondrial membrane components and respiratory chain NADH dehydrogenase. Study of the mitochondrial activity of TMX2-deficient fibroblasts suggested reduced respiratory reserve capacity, compensated by increased glycolytic activity. TMX2 occurs in both reduced and oxidized monomeric form. It also forms (homo)dimers with the ratio of dimers/monomers increasing under conditions of oxidative stress. Variant TMX2 increased propensity to form dimers, thus mimicking increased oxidative state. This was observed under stress but also under native conditions. ---------; Changed rating: GREEN |
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| Limb disorders v1.129 | IHH | Eleanor Williams Phenotypes for gene: IHH were changed from Acrocapitofemoral dysplasia 607778; Brachydactyly, type A1 112500; syndactyly and craniosynostosis to Acrocapitofemoral dysplasia 607778; Brachydactyly, type A1 112500; syndactyly and craniosynostosis; F syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.128 | IHH | Eleanor Williams Publications for gene: IHH were set to 21167467 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.127 | IHH | Eleanor Williams commented on gene: IHH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.84 | ATAD1 | Rebecca Foulger Phenotypes for gene: ATAD1 were changed from Hyperekplexia 4 to Hyperekplexia 4, 618011 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.83 | ERCC5 | Rebecca Foulger Phenotypes for gene: ERCC5 were changed from Cerebrooculofacioskeletal syndrome 3 to Cerebrooculofacioskeletal syndrome 3, 616570 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.82 | ERCC1 | Rebecca Foulger Phenotypes for gene: ERCC1 were changed from Cerebrooculofacioskeletal syndrome 4 to Cerebrooculofacioskeletal syndrome 4, 610758 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.81 | CEP55 | Rebecca Foulger Phenotypes for gene: CEP55 were changed from Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly, 236500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.80 | DHCR24 | Rebecca Foulger Phenotypes for gene: DHCR24 were changed from dermosterolsis to Dermosterolsis, 602398 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.79 | ALG3 | Rebecca Foulger Phenotypes for gene: ALG3 were changed from Congenital disorder of glycosylation, type Id to Congenital disorder of glycosylation, type Id, 601110 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.78 | TRIP4 | Rebecca Foulger Phenotypes for gene: TRIP4 were changed from Spinal muscular atrophy with congenital bone fractures 1 to Spinal muscular atrophy with congenital bone fractures 1, 616866 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.77 | GFM2 | Rebecca Foulger Phenotypes for gene: GFM2 were changed from Combined oxidative phosphorylation deficiency 39, 618397 to Combined oxidative phosphorylation deficiency 39, 618397; arthrogryposis multiplex congenita | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.76 | CACNA1E | Rebecca Foulger Classified gene: CACNA1E as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.76 | CACNA1E | Rebecca Foulger Added comment: Comment on list classification: Promoted to Amber awaiting clinical review: PMID:30343943 (Helbig et al., 2018) identified 30 unrelated individuals with missense variants in CACNA1E. 13/30 (43%) affected individuals had congenital joint contractures ranging from isolated talipes equinovarus to arthrogryposis multiplex congenita. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.76 | CACNA1E | Rebecca Foulger Gene: cacna1e has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.75 | CACNA1E | Rebecca Foulger Phenotypes for gene: CACNA1E were changed from Epileptic encephalopathy, early infantile, 69, 618285 to Epileptic encephalopathy, early infantile, 69, 618285; congenital joint contractures | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.74 | CACNA1E | Rebecca Foulger Mode of inheritance for gene: CACNA1E was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.73 | CACNA1E | Rebecca Foulger Phenotypes for gene: CACNA1E were changed from to Epileptic encephalopathy, early infantile, 69, 618285 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.72 | CACNA1E | Rebecca Foulger Publications for gene: CACNA1E were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.71 | GFM2 | Rebecca Foulger Classified gene: GFM2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.71 | GFM2 | Rebecca Foulger Added comment: Comment on list classification: Demoted to Amber awaiting clinical review: limited evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.71 | GFM2 | Rebecca Foulger Gene: gfm2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.70 | GFM2 | Rebecca Foulger Mode of inheritance for gene: GFM2 was changed from MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.69 | GFM2 | Rebecca Foulger Publications for gene: GFM2 were set to 30343943 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.68 | GFM2 | Rebecca Foulger Phenotypes for gene: GFM2 were changed from Epileptic encephalopathy, early infantile, 69 to Combined oxidative phosphorylation deficiency 39, 618397 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.354 | ALG3 | Rebecca Foulger Publications for gene: ALG3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | TACO1 | Matthew Edwards reviewed gene: TACO1: Rating: RED; Mode of pathogenicity: None; Publications: 27319982, 19503089; Phenotypes: Mitochondrial complex IV deficiency; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | TAB2 | Matthew Edwards reviewed gene: TAB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 20493459; Phenotypes: OMIM 614980 Congenital heart defects, nonsyndromic, 2; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | SPRED1 | Matthew Edwards reviewed gene: SPRED1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Legius syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | SGCD | Matthew Edwards reviewed gene: SGCD: Rating: AMBER; Mode of pathogenicity: None; Publications: 18779423, 23900355, 10735275; Phenotypes: OMIM 606685 Cardiomyopathy, dilated, 1L, 601287 Muscular dystrophy, limb-girdle, autosomal recessive 6; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | SDHAF1 | Matthew Edwards changed review comment from: None of the literature describes cardian involvement, and a cardiomyopathy is not going to be presenting feature (key symptom is leukoencephalopathy). Not appropriate for this panel.; to: None of the literature describes cardiac involvement, and a cardiomyopathy (even if present) is not going to be presenting feature (key symptom is leukoencephalopathy). Not appropriate for this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | SDHAF1 | Matthew Edwards reviewed gene: SDHAF1: Rating: RED; Mode of pathogenicity: None; Publications: 22995659, 26642834, 19465911; Phenotypes: OMIM 252011 Mitochondrial complex II deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | PPP1CB | Matthew Edwards changed review comment from: Several literature reports with good evidence for causation. Noonan-like syndrome has congenitall heart abnormalities (restricted to structural abnormalities, no reports of HCM), so gene isappropriate for this panel on bais of congential cardiac abnormalities.; to: Several literature reports with good evidence for causation. Noonan-like syndrome has congenitall heart abnormalities (restricted to structural abnormalities, no reports of HCM), so gene is appropriate for this panel on basis of congential cardiac abnormalities if panel is meant to encompass Rasopathies | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | PPP1CB | Matthew Edwards reviewed gene: PPP1CB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27264673, 28211982, 27681385; Phenotypes: OMIM 617506 Noonan syndrome-like disorder with loose anagen hair 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.127 | SOX9 |
Eleanor Williams changed review comment from: Associated with Campomelic dysplasia (114290) in OMIM and CAMPOMELIC DYSPLASIA and PIERRE ROBIN SEQUENCE in Gene2Phenotype (both confirmed). Publications relating to the duplications in the region between KCNJ2 and SOX9: PMID: 19639023 - Kurth et al 2009 - investigated four families with symmetric brachydactyly of the hands and feet as well as hyponychia or anonychia. All affected were of normal height and had no other skeletal abnormality. They identified overlapping duplications in a ∼2 Mb interval on chromosome 17q24.3. Comparison of the four duplications revealed a minimal critical region of ∼1.2 Mb encompassing a large gene desert between KCNJ2 and SOX9. In situ hybridizations in mouse embryos, showed that Sox9 was strongly expressed in the distal mesenchymal condensations at embryonic day (E) 12.5 that will later develop into the terminal phalanges and, at a later time point (E17.5), in the anlagen of the developing claw. PMID: 27706140 - Franke et al 2016 - used chromosome conformation capture methods to look at topologically associated domains in patient cells and mouse models where the regulatory region next to SOX9 is duplicated. They generated mice with a duplicated region associated with Cooks syndrome as reported by Kurth et al 2009 (which they call Dup-C). cHi-C of E12.5 Dup-C limb buds showed a new chromatin domain corresponding to the duplicated region. RNA sequencing expression analysis of Dup-C limb buds at E12.5 and E17.5 confirmed the upregulation of Kcnj2, whereas other genes around the locus stayed unchanged, in particular Sox9, but also Kcnj16. Thus, the inclusion of Kcnj2 in the neo-TAD resulted in its activation by regulatory elements that originally belonged to the Sox9 TAD. Other publications. PMID: 21373255 - Corbani et al 2011 - reported patient with SOX9 missense mutation and mild form of campomelic dysplasia. Features include short stature, dysmorphic facial features, limitation of supination and pronation of the forearms, dysplastic nails, and bone abnormalities consisting especially of cone-shaped epiphyses of the middle phalanx of the 2nd fingers, brachydactyly and clinodactyly of the middle phalanx of both 5th fingers, short 4th metacarpals, radial and femoral head subluxation, hypoplastic scapulae, humeral and ulnar epiphyseal abnormalities, unossified symphysis pubis, and a significant delay in bone age. PMID: 24704791 - Takenouchi et al 2014 - report patient with many features of the type 2 collagen disorder including micrognathia, cleft palate, flat midface, and visual and hearing impairment, and a retarded enchondral ossification of the appendicular skeleton during the infantile period. The patient had in addition severe developmental delay. A de novo heterozygous missense mutation, c.239T>G p.Val80Gly, in exon 1 of SOX9 was found. Summary: Evidence that duplication of a region upstream of SOX9 can result in a brachydactyly phenotype. This appears to be as a result of increased expression of KCNJ2. It maybe most appropriate to add this upstream region as a CNV.; to: Associated with Campomelic dysplasia (114290) in OMIM and CAMPOMELIC DYSPLASIA and PIERRE ROBIN SEQUENCE in Gene2Phenotype (both confirmed). Publications relating to the duplications in the region between KCNJ2 and SOX9: PMID: 19639023 - Kurth et al 2009 - investigated four families with symmetric brachydactyly of the hands and feet as well as hyponychia or anonychia. All affected were of normal height and had no other skeletal abnormality. They identified overlapping duplications in a ∼2 Mb interval on chromosome 17q24.3. Comparison of the four duplications revealed a minimal critical region of ∼1.2 Mb encompassing a large gene desert between KCNJ2 and SOX9. In situ hybridizations in mouse embryos, showed that Sox9 was strongly expressed in the distal mesenchymal condensations at embryonic day (E) 12.5 that will later develop into the terminal phalanges and, at a later time point (E17.5), in the anlagen of the developing claw. PMID: 27706140 - Franke et al 2016 - used chromosome conformation capture methods to look at topologically associated domains in patient cells and mouse models where the regulatory region next to SOX9 is duplicated. They generated mice with a duplicated region associated with Cooks syndrome as reported by Kurth et al 2009 (which they call Dup-C). cHi-C of E12.5 Dup-C limb buds showed a new chromatin domain corresponding to the duplicated region. RNA sequencing expression analysis of Dup-C limb buds at E12.5 and E17.5 confirmed the upregulation of Kcnj2, whereas other genes around the locus stayed unchanged, in particular Sox9, but also Kcnj16. Thus, the inclusion of Kcnj2 in the neo-TAD resulted in its activation by regulatory elements that originally belonged to the Sox9 TAD. Other publications report SNVs and deletions of SOX9 in association with Campomelic dysplasia Summary: Evidence that duplication of a region upstream of SOX9 can result in a brachydactyly phenotype. This appears to be as a result of increased expression of KCNJ2. It maybe most appropriate to add this upstream region as a CNV. |
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| Arthrogryposis v2.67 | SLC6A9 | Rebecca Foulger Classified gene: SLC6A9 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.67 | SLC6A9 | Rebecca Foulger Added comment: Comment on list classification: Rated SLC6A9 Amber in consultation with Zerin Hyder (Genomics England Clinical Team) based on literature cases (PMIDs 27773429, 27481395), and a Probable rating for an Arthrogryposis disorder in Gene2Phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.67 | SLC6A9 | Rebecca Foulger Gene: slc6a9 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.127 | EIF4A3 |
Eleanor Williams changed review comment from: PMID: 10594883 - Walter-Nicolet et al 1999 - report a French boy with phenotype similar to Richieri-Costa and Pereira form of acrofacial dysostosis but no genome analysis done. PMID: 29112243 - Bertola et al 2018 - describe 5 (4 Brasilian, one from England, of African ancestry) new individuals with Richieri-Costa-Pereira syndrome. The patient from England/Kenya showed limb abnormalities of Hypoplastic hallux and club feet only. Expansions of the repeated motif in the 5′ UTR of EIF4A3 were found in all individuals and ranged from 14 to 16 repeats.; to: Additional cases: PMID: 10594883 - Walter-Nicolet et al 1999 - report a French boy with phenotype similar to Richieri-Costa and Pereira form of acrofacial dysostosis but no genome analysis done. PMID: 29112243 - Bertola et al 2018 - describe 5 (4 Brasilian, one from England, of African ancestry) new individuals with Richieri-Costa-Pereira syndrome. The patient from England/Kenya showed limb abnormalities of Hypoplastic hallux and club feet only. Expansions of the repeated motif in the 5′ UTR of EIF4A3 were found in all individuals and ranged from 14 to 16 repeats. |
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| Limb disorders v1.127 | EIF4A3 |
Eleanor Williams changed review comment from: PMID: 10594883 - Walter-Nicolet et al 1999 - report a French boy with phenotype similar to Richieri-Costa and Pereira form of acrofacial dysostosis but no genome analysis done. PMID: 29112243 - Bertola et al 2018 - describe 5 (4 Brasilian, one from England, of African ancestry) new individuals with Richieri-Costa-Pereira syndrome, including a patient from England, of African ancestry. The patient from England/Kenya showed limb abnormalities of Hypoplastic hallux and club feet only. Expansions of the repeated motif in the 5′ UTR of EIF4A3 were found in all individuals and ranged from 14 to 16 repeats.; to: PMID: 10594883 - Walter-Nicolet et al 1999 - report a French boy with phenotype similar to Richieri-Costa and Pereira form of acrofacial dysostosis but no genome analysis done. PMID: 29112243 - Bertola et al 2018 - describe 5 (4 Brasilian, one from England, of African ancestry) new individuals with Richieri-Costa-Pereira syndrome. The patient from England/Kenya showed limb abnormalities of Hypoplastic hallux and club feet only. Expansions of the repeated motif in the 5′ UTR of EIF4A3 were found in all individuals and ranged from 14 to 16 repeats. |
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| Early onset or syndromic epilepsy v1.475 | IDH2 | Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green.Refers to glioma patients: not a seizure disorder. Demoted from Green to RED.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Refers to glioma patients- not a seizure disorder. Demoted from Green to RED. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.127 | LMBR1 |
Eleanor Williams changed review comment from: Variants within LMBR1 coding sequence: PMID:11090342 - Ianakiev et al - 2001- found a genomic 4- to 6-kb deletion in LMBR1 in 5 unrelated Brazilian families with acheiropody. The deletion led to a trascript lacking exon 4 and introducing a premature stop codon downstream of exon 3. Haplotype analysis confirmed the expectation that a single common ancestral mutation was the cause of all the cases. PMID: 26749485 - Shamseldin et al 2016 - patient with acheiropodia who had a nullizygous deletion of 102 kb spanning LMBR1. The ZRS is a sonic hedgehog (SHH) regulatory region of approx 800bp. It is not thought to affect the expression LMBR1. Variants and duplications affecting the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene: Numerous reports of heterozygous variants in ZRS being associated with preaxial polydactyly/Werner mesomelic syndrome - (PMID: 31395945 - Xu et al 2019 - 1 case, 446T>A ZRS), (PMID: 19847792 Wieczorek et al. (2010) - 2 cases with variants 404G>A and 404G>C ZRS), (PMID: 24965254 Norbnop et al. (2014) - 2 cases, one familial and one sporadic with 406A>G and 404G>A ZRS variants), (PMID: 24777739 - VanderMeer et al. (2014) - 1 case - 5 generation family with a c.402C->T variant (A more severely affected daughter was homozygous for the same mutation)). Other cases listed in OMIM. PMID: 28127823 - Xiang et al 2017 - report 6/102 of patients with preaxial polydactyly type I with variants in a region upstream of the ZRS. Reports of duplications covering parts of the ZRS also being associated with a limb phenotype. PMID: 19847792 - Wieczorek et al. (2010) - report 2 families (families 3 and 4) with duplications (73-kb and 276-kb) affecting the ZRS region. Members of family 3 had Haas type polysyndactyly and family 4 had triphalangeal thumb-polysyndactyly syndrome. PMID: 18178630 - Klopocki et al 2008 - report a large 4-generation pedigree with variable triphalangeal thumb and polysyndactyly, No point mutations found in the LMBR1 gene but array CGH analysis identified a heterozygous 589-kb duplication comprising the ZRS. PMID: 18417549 - Sun et al 2009 - in 6 Han Chinese families with Triphalangeal thumb-polysyndactyly syndrome they identified duplications of ZRS which segregated with the limb phenotypes in all families. PMID: 19291772 - Wu et al 2009 - in a Chinese family with type IV syndactyly and tibial hypoplasia they detected a duplication of between 105 to 115 kb. PMID: 24456159 - Lohan et al 2104 - report on 5 unrelated families with overlapping microduplications encompassing the ZPA regulatory sequence. Larger duplications of the ZRS region (>80 kb) are associated with Haas-type polysyndactyly, whereas smaller duplications (<80 kb) result in a Laurin-Sandrow syndrome phenotype. Summary: > 3 cases where SNVs in the ZRS are found in patients with polydactyly. In >3 cases duplications covering parts of the ZRS were found in patients with a limb phenotype. Currently variants in the ZRS would NOT be reported via WGS. Duplications > 10Kb covering the LMBR1 gene would be picked up as the gene is green.; to: Variants within LMBR1 coding sequence: PMID:11090342 - Ianakiev et al - 2001- found a genomic 4- to 6-kb deletion in LMBR1 in 5 unrelated Brazilian families with acheiropody. The deletion led to a trascript lacking exon 4 and introducing a premature stop codon downstream of exon 3. Haplotype analysis confirmed the expectation that a single common ancestral mutation was the cause of all the cases. PMID: 26749485 - Shamseldin et al 2016 - patient with acheiropodia who had a nullizygous deletion of 102 kb spanning LMBR1. The ZRS (zone of polarizing activity regulatory sequence) is a sonic hedgehog (SHH) regulatory region of approx 800bp. It is not thought to affect the expression LMBR1. Variants and duplications affecting the ZRS within intron 5 of the LMBR1 gene: Numerous reports of heterozygous variants in ZRS being associated with preaxial polydactyly/Werner mesomelic syndrome - (PMID: 31395945 - Xu et al 2019 - 1 case, 446T>A ZRS), (PMID: 19847792 Wieczorek et al. (2010) - 2 cases with variants 404G>A and 404G>C ZRS), (PMID: 24965254 Norbnop et al. (2014) - 2 cases, one familial and one sporadic with 406A>G and 404G>A ZRS variants), (PMID: 24777739 - VanderMeer et al. (2014) - 1 case - 5 generation family with a c.402C->T variant (A more severely affected daughter was homozygous for the same mutation)). Other cases listed in OMIM. PMID: 28127823 - Xiang et al 2017 - report 6/102 of patients with preaxial polydactyly type I with variants in a region upstream of the ZRS. Reports of duplications covering parts of the ZRS also being associated with a limb phenotype. PMID: 19847792 - Wieczorek et al. (2010) - report 2 families (families 3 and 4) with duplications (73-kb and 276-kb) affecting the ZRS region. Members of family 3 had Haas type polysyndactyly and family 4 had triphalangeal thumb-polysyndactyly syndrome. PMID: 18178630 - Klopocki et al 2008 - report a large 4-generation pedigree with variable triphalangeal thumb and polysyndactyly, No point mutations found in the LMBR1 gene but array CGH analysis identified a heterozygous 589-kb duplication comprising the ZRS. PMID: 18417549 - Sun et al 2009 - in 6 Han Chinese families with Triphalangeal thumb-polysyndactyly syndrome they identified duplications of ZRS which segregated with the limb phenotypes in all families. PMID: 19291772 - Wu et al 2009 - in a Chinese family with type IV syndactyly and tibial hypoplasia they detected a duplication of between 105 to 115 kb. PMID: 24456159 - Lohan et al 2104 - report on 5 unrelated families with overlapping microduplications encompassing the ZPA regulatory sequence. Larger duplications of the ZRS region (>80 kb) are associated with Haas-type polysyndactyly, whereas smaller duplications (<80 kb) result in a Laurin-Sandrow syndrome phenotype. Summary: > 3 cases where SNVs in the ZRS are found in patients with polydactyly. In >3 cases duplications covering parts of the ZRS were found in patients with a limb phenotype. Currently variants in the ZRS would NOT be reported via WGS. Duplications > 10Kb covering the LMBR1 gene would be picked up as the gene is green. |
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| Early onset or syndromic epilepsy v1.475 | CYP27A1 | Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. prominent phenotype is dystonia/ataxia. Demoted from Green to Amber.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Prominent phenotype is dystonia/ataxia. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1122 | WDFY3 | Ivone Leong Classified gene: WDFY3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1122 | WDFY3 | Ivone Leong Added comment: Comment on list classification: Gene promoted from Red to Amber based on evidence provided by expert reviewer. All affected individuals have mild-moderate ID, therefore the gene has been rated Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1122 | WDFY3 | Ivone Leong Gene: wdfy3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.353 | LMBR1 | Eleanor Williams commented on gene: LMBR1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1121 | WDFY3 | Ivone Leong Publications for gene: WDFY3 were set to 27008544 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.475 | SCN9A | Rebecca Foulger Publications for gene: SCN9A were set to 19763161; 29500686 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.244 | LMBR1 | Eleanor Williams commented on gene: LMBR1: Reported microduplications in LMBR1 associated with Laurin-Sandrow syndrome are in the SHH regulatory element (ZRS) that resides in intron 5 of the LMBR1 gene. Duplications are >10kb and therefore the current pipeline should report these as CNVs within a green gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.474 | FLNA | Rebecca Foulger changed review comment from: Comment on mode of inheritance: At the Webex call 22nd November 2019, it was notes that want to target FEMALES ONLY for the Heterotopia periventricular phenotype.; to: Comment on mode of inheritance: At the Webex call 22nd November 2019, it was noted that want to target FEMALES ONLY for the Heterotopia periventricular phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Radial dysplasia v1.6 | LMBR1 | Eleanor Williams commented on gene: LMBR1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.127 | LMBR1 |
Eleanor Williams changed review comment from: Variants within LMBR1 coding sequence: PMID:11090342 - Ianakiev et al - 2001- found a genomic 4- to 6-kb deletion in LMBR1 in 5 unrelated Brazilian families with acheiropody. The deletion led to a trascript lacking exon 4 and introducing a premature stop codon downstream of exon 3. Haplotype analysis confirmed the expectation that a single common ancestral mutation was the cause of all the cases. PMID: 26749485 - Shamseldin et al 2016 - patient with acheiropodia who had a nullizygous deletion of 102 kb spanning LMBR1. The ZRS is a sonic hedgehog (SHH) regulatory region of approx 800bp. It is not thought to affect the expression LMBR1. Variants and duplications affecting the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene: Numerous reports of heterozygous variants in ZRS being associated with preaxial polydactyly/Werner mesomelic syndrome - (PMID: 31395945 - Xu et al 2019 - 1 case, 446T>A ZRS), (PMID: 19847792 Wieczorek et al. (2010) - 2 cases with variants 404G>A and 404G>C ZRS), (PMID: 24965254 Norbnop et al. (2014) - 2 cases, one familial and one sporadic with 406A>G and 404G>A ZRS variants), (PMID: 24777739 - VanderMeer et al. (2014) - 1 case - 5 generation family with a c.402C->T variant (A more severely affected daughter was homozygous for the same mutation)). Other cases listed in OMIM. PMID: 28127823 - Xiang et al 2017 - report 6/102 of patients with preaxial polydactyly type I with variants in a region upstream of the ZRS. Reports of duplications covering parts of the ZRS also being associated with a limb phenotype. PMID: 19847792 - Wieczorek et al. (2010) - report 2 families (families 3 and 4) with duplications (73-kb and 276-kb) affecting the ZRS region. Members of family 3 had Haas type polysyndactyly and family 4 had triphalangeal thumb-polysyndactyly syndrome. PMID: 18178630 - Klopocki et al 2008 - report a large 4-generation pedigree with variable triphalangeal thumb and polysyndactyly, No point mutations found in the LMBR1 gene but array CGH analysis identified a heterozygous 589-kb duplication comprising the ZRS. PMID: 18417549 - Sun et al 2009 - in 6 Han Chinese families with Triphalangeal thumb-polysyndactyly syndrome they identified duplications of ZRS which segregated with the limb phenotypes in all families. PMID: 19291772 - Wu et al 2009 - in a Chinese family with type IV syndactyly and tibial hypoplasia they detected a duplication of between 105 to 115 kb. Summary: > 3 cases where SNVs in the ZRS are found in patients with polydactyly. In >3 cases duplications covering parts of the ZRS were found in patients with a limb phenotype. Currently variants in the ZRS would NOT be reported via WGS. Duplications > 10Kb covering the LMBR1 gene would be picked up as the gene is green.; to: Variants within LMBR1 coding sequence: PMID:11090342 - Ianakiev et al - 2001- found a genomic 4- to 6-kb deletion in LMBR1 in 5 unrelated Brazilian families with acheiropody. The deletion led to a trascript lacking exon 4 and introducing a premature stop codon downstream of exon 3. Haplotype analysis confirmed the expectation that a single common ancestral mutation was the cause of all the cases. PMID: 26749485 - Shamseldin et al 2016 - patient with acheiropodia who had a nullizygous deletion of 102 kb spanning LMBR1. The ZRS is a sonic hedgehog (SHH) regulatory region of approx 800bp. It is not thought to affect the expression LMBR1. Variants and duplications affecting the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene: Numerous reports of heterozygous variants in ZRS being associated with preaxial polydactyly/Werner mesomelic syndrome - (PMID: 31395945 - Xu et al 2019 - 1 case, 446T>A ZRS), (PMID: 19847792 Wieczorek et al. (2010) - 2 cases with variants 404G>A and 404G>C ZRS), (PMID: 24965254 Norbnop et al. (2014) - 2 cases, one familial and one sporadic with 406A>G and 404G>A ZRS variants), (PMID: 24777739 - VanderMeer et al. (2014) - 1 case - 5 generation family with a c.402C->T variant (A more severely affected daughter was homozygous for the same mutation)). Other cases listed in OMIM. PMID: 28127823 - Xiang et al 2017 - report 6/102 of patients with preaxial polydactyly type I with variants in a region upstream of the ZRS. Reports of duplications covering parts of the ZRS also being associated with a limb phenotype. PMID: 19847792 - Wieczorek et al. (2010) - report 2 families (families 3 and 4) with duplications (73-kb and 276-kb) affecting the ZRS region. Members of family 3 had Haas type polysyndactyly and family 4 had triphalangeal thumb-polysyndactyly syndrome. PMID: 18178630 - Klopocki et al 2008 - report a large 4-generation pedigree with variable triphalangeal thumb and polysyndactyly, No point mutations found in the LMBR1 gene but array CGH analysis identified a heterozygous 589-kb duplication comprising the ZRS. PMID: 18417549 - Sun et al 2009 - in 6 Han Chinese families with Triphalangeal thumb-polysyndactyly syndrome they identified duplications of ZRS which segregated with the limb phenotypes in all families. PMID: 19291772 - Wu et al 2009 - in a Chinese family with type IV syndactyly and tibial hypoplasia they detected a duplication of between 105 to 115 kb. PMID: 24456159 - Lohan et al 2104 - report on 5 unrelated families with overlapping microduplications encompassing the ZPA regulatory sequence. Larger duplications of the ZRS region (>80 kb) are associated with Haas-type polysyndactyly, whereas smaller duplications (<80 kb) result in a Laurin-Sandrow syndrome phenotype. Summary: > 3 cases where SNVs in the ZRS are found in patients with polydactyly. In >3 cases duplications covering parts of the ZRS were found in patients with a limb phenotype. Currently variants in the ZRS would NOT be reported via WGS. Duplications > 10Kb covering the LMBR1 gene would be picked up as the gene is green. |
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| Early onset or syndromic epilepsy v1.474 | PEX6 | Rebecca Foulger Classified gene: PEX6 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.474 | PEX6 | Rebecca Foulger Gene: pex6 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.473 | PEX6 | Rebecca Foulger commented on gene: PEX6: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that PEX genes are better tested through the metabolic panel, and should be demoted to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.473 | PEX3 | Rebecca Foulger Classified gene: PEX3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.473 | PEX3 | Rebecca Foulger Gene: pex3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.472 | PEX3 | Rebecca Foulger commented on gene: PEX3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that PEX genes are better tested through the metabolic panel, and should be demoted to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.472 | PEX2 | Rebecca Foulger Classified gene: PEX2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.472 | PEX2 | Rebecca Foulger Gene: pex2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.471 | PEX2 | Rebecca Foulger commented on gene: PEX2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that PEX genes are better tested through the metabolic panel, and should be demoted to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.471 | PEX19 | Rebecca Foulger Classified gene: PEX19 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.471 | PEX19 | Rebecca Foulger Gene: pex19 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.470 | PEX19 | Rebecca Foulger commented on gene: PEX19: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that PEX genes are better tested through the metabolic panel, and should be demoted to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.470 | PEX13 | Rebecca Foulger Classified gene: PEX13 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.470 | PEX13 | Rebecca Foulger Gene: pex13 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.469 | PEX13 | Rebecca Foulger commented on gene: PEX13: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that PEX genes are better tested through the metabolic panel, and should be demoted to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1120 | IQSEC1 | Catherine Snow Classified gene: IQSEC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1120 | IQSEC1 | Catherine Snow Gene: iqsec1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1119 | IQSEC1 | Catherine Snow reviewed gene: IQSEC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31607425; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.66 | MAGEL2 | Rebecca Foulger Publications for gene: MAGEL2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.65 | MAGEL2 | Rebecca Foulger commented on gene: MAGEL2: G2P phenotype is 'ARTHROGRYPOSIS MULTIPLEX CONGENITA' with 'probable' disease confidence, in addition to 'Schaaf-Yang syndrome' with confirmed confidence. G2P rating based on PMID:26365340 who report 2 families with lethal arthrogryposis in deceased fetuses and MAGEL2 variant. PMID:27195816 (Fountain et al., 2017) identified the same heterozygous c.1996delC variant in 2 fetal siblings with Shaaf-Yang syndrome manifesting as AMC. PMID:31504653 (Gregory et al., 2019) report 5 patients (4 families), 3 of whom had arthrogryposis and the Gln666SerfsTer36 MAGEL2 variant. Additional papers reporting arthrogryposis as part of Schaaf-Yang syndrome E.g. PMID:29359444 so likely to be the same condition with variable severity/phenotype. Sufficient cases of arthrogryposis in the literature for a Green rating on Arthrogryposis panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.65 | SLC6A9 | Rebecca Foulger Publications for gene: SLC6A9 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | SLC6A9 | Rebecca Foulger commented on gene: SLC6A9: Gene2Phenotype phenotype of 'Glycine Encephalopathy with Arthrogryposis' with 'probable' disease confidence based on PMID:27773429 (Kurolap et al., 2016) who report 4 individuals from 2 Arab-Muslim families with arthrogryposis amongst their symptoms. In addition, PMID:27481395 (Alfadhel et al., 2016) report a consanguineous family with one child who presented with non-ketotic hyperglycinemia and a homozygous missense variant in SLC6A9 (p.Ser407Gly). Features included joint laxity but Arthrogryposis isn't mentioned specifically. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | SLC6A9 | Rebecca Foulger changed review comment from: Added to Arthrogryposis panel after agreement with Zerin Hyder (Genomics England Clinical Team), based on Arthrogryposis phenotye on DDG2P panel V1.154.; to: Added to Arthrogryposis panel after agreement with Zerin Hyder (Genomics England Clinical Team), based on Arthrogryposis phenotype on DDG2P panel V1.154. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | VAMP1 | Rebecca Foulger reviewed gene: VAMP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | MYL1 | Rebecca Foulger reviewed gene: MYL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | SMN1 | Rebecca Foulger reviewed gene: SMN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | GFM2 | Rebecca Foulger reviewed gene: GFM2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | CACNA1E | Rebecca Foulger reviewed gene: CACNA1E: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | CCDC47 | Rebecca Foulger reviewed gene: CCDC47: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | PIGS | Rebecca Foulger reviewed gene: PIGS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | EXOSC9 | Rebecca Foulger reviewed gene: EXOSC9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | ATAD1 | Rebecca Foulger reviewed gene: ATAD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | TBCD | Rebecca Foulger reviewed gene: TBCD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | TRIP4 | Rebecca Foulger reviewed gene: TRIP4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | ERCC5 | Rebecca Foulger reviewed gene: ERCC5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | KIF5C | Rebecca Foulger reviewed gene: KIF5C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | C12orf65 | Rebecca Foulger reviewed gene: C12orf65: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | CHMP1A | Rebecca Foulger reviewed gene: CHMP1A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | ERCC1 | Rebecca Foulger reviewed gene: ERCC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | CEP55 | Rebecca Foulger reviewed gene: CEP55: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | DHCR24 | Rebecca Foulger reviewed gene: DHCR24: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | ALG3 | Rebecca Foulger reviewed gene: ALG3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | ZNF335 | Rebecca Foulger reviewed gene: ZNF335: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | SLC6A9 | Rebecca Foulger reviewed gene: SLC6A9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.64 | MAGEL2 | Rebecca Foulger reviewed gene: MAGEL2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1119 | SVBP | Catherine Snow Phenotypes for gene: SVBP were changed from Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, 618569 to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, 618569 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1119 | SVBP | Catherine Snow Mode of inheritance for gene: SVBP was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1119 | SVBP | Catherine Snow Phenotypes for gene: SVBP were changed from Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, 618569 to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, 618569 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1119 | SVBP | Catherine Snow Publications for gene: SVBP were set to 26350204; 31363758; 30607023 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1119 | SVBP | Catherine Snow Phenotypes for gene: SVBP were changed from to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, 618569 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1118 | SVBP | Catherine Snow Publications for gene: SVBP were set to 26350204 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1118 | SVBP | Catherine Snow Mode of inheritance for gene: SVBP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1117 | SVBP | Catherine Snow reviewed gene: SVBP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, 618569; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.63 | VAMP1 |
Rebecca Foulger gene: VAMP1 was added gene: VAMP1 was added to Arthrogryposis. Sources: Other,Expert Review Green Mode of inheritance for gene: VAMP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VAMP1 were set to 28168212; 28253535 Phenotypes for gene: VAMP1 were set to presynaptic CMS; Congenital myasthenic syndrome |
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| Arthrogryposis v2.63 | MYL1 |
Rebecca Foulger gene: MYL1 was added gene: MYL1 was added to Arthrogryposis. Sources: Other,Expert Review Green Mode of inheritance for gene: MYL1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MYL1 were set to congenital myopathy |
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| Limb disorders v1.127 | SHH | Eleanor Williams changed review comment from: Variants and duplications in the ZRS region within intron LMBR1 which affect the expression of SHH have been reviewed in gene LMBR1 on this panel.; to: Variants and duplications in the regulatory ZRS region within intron LMBR1 which affect the expression of SHH have been reviewed in gene LMBR1 on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.127 | SHH | Eleanor Williams commented on gene: SHH: Variants and duplications in the ZRS region within intron LMBR1 which affect the expression of SHH have been reviewed in gene LMBR1 on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1117 | NSF | Ivone Leong Classified gene: NSF as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1117 | NSF | Ivone Leong Added comment: Comment on list classification: New gene submitted by expert reviewed. Based on the evidence provided it was decided that there is currently not enough evidence to establish a gene-phenotype association. Therefore, this gene has been given a Red rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1117 | NSF | Ivone Leong Gene: nsf has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1116 | KCNT2 | Ivone Leong Classified gene: KCNT2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1116 | KCNT2 | Ivone Leong Added comment: Comment on list classification: New gene submitted by expert reviewer. Based on the evidence provided it was decided that there is enough evidence for this gene to be given Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1116 | KCNT2 | Ivone Leong Gene: kcnt2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.62 | SMN1 |
Rebecca Foulger gene: SMN1 was added gene: SMN1 was added to Arthrogryposis. Sources: Literature,Expert Review Green Mode of inheritance for gene: SMN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMN1 were set to 27911332; 10700538; 11826188 Phenotypes for gene: SMN1 were set to arthrogryposis; SMA 0 |
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| Arthrogryposis v2.62 | GFM2 |
Rebecca Foulger gene: GFM2 was added gene: GFM2 was added to Arthrogryposis. Sources: Literature,Expert Review Green Mode of inheritance for gene: GFM2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Publications for gene: GFM2 were set to 30343943 Phenotypes for gene: GFM2 were set to Epileptic encephalopathy, early infantile, 69 |
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| Arthrogryposis v2.62 | CACNA1E |
Rebecca Foulger gene: CACNA1E was added gene: CACNA1E was added to Arthrogryposis. Sources: Expert Review Red Mode of inheritance for gene: CACNA1E was set to |
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| Arthrogryposis v2.62 | CCDC47 |
Rebecca Foulger gene: CCDC47 was added gene: CCDC47 was added to Arthrogryposis. Sources: Expert Review Red Mode of inheritance for gene: CCDC47 was set to |
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| Arthrogryposis v2.62 | PIGS |
Rebecca Foulger gene: PIGS was added gene: PIGS was added to Arthrogryposis. Sources: Expert Review Red Mode of inheritance for gene: PIGS was set to |
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| Arthrogryposis v2.62 | EXOSC9 |
Rebecca Foulger gene: EXOSC9 was added gene: EXOSC9 was added to Arthrogryposis. Sources: Expert Review Red Mode of inheritance for gene: EXOSC9 was set to |
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| Arthrogryposis v2.62 | ATAD1 |
Rebecca Foulger gene: ATAD1 was added gene: ATAD1 was added to Arthrogryposis. Sources: Literature,Expert Review Green Mode of inheritance for gene: ATAD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATAD1 were set to 29659736; 28180185; 29390050 Phenotypes for gene: ATAD1 were set to Hyperekplexia 4 |
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| Arthrogryposis v2.62 | SLC6A9 |
Rebecca Foulger Source Expert Review Red was added to SLC6A9. Rating Changed from Green List (high evidence) to Red List (low evidence) |
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| Arthrogryposis v2.62 | TBCD |
Rebecca Foulger gene: TBCD was added gene: TBCD was added to Arthrogryposis. Sources: Expert Review Red Mode of inheritance for gene: TBCD was set to |
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| Arthrogryposis v2.62 | TRIP4 |
Rebecca Foulger gene: TRIP4 was added gene: TRIP4 was added to Arthrogryposis. Sources: Literature,Expert Review Amber Mode of inheritance for gene: TRIP4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRIP4 were set to 26924529 Phenotypes for gene: TRIP4 were set to Spinal muscular atrophy with congenital bone fractures 1 |
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| Arthrogryposis v2.62 | ERCC5 |
Rebecca Foulger gene: ERCC5 was added gene: ERCC5 was added to Arthrogryposis. Sources: Literature,Expert Review Amber Mode of inheritance for gene: ERCC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERCC5 were set to 9096355; 24700531 Phenotypes for gene: ERCC5 were set to Cerebrooculofacioskeletal syndrome 3 |
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| Arthrogryposis v2.62 | KIF5C |
Rebecca Foulger gene: KIF5C was added gene: KIF5C was added to Arthrogryposis. Sources: Expert Review Red Mode of inheritance for gene: KIF5C was set to |
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| Arthrogryposis v2.62 | C12orf65 |
Rebecca Foulger gene: C12orf65 was added gene: C12orf65 was added to Arthrogryposis. Sources: Expert Review Red Mode of inheritance for gene: C12orf65 was set to |
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| Arthrogryposis v2.62 | CHMP1A |
Rebecca Foulger gene: CHMP1A was added gene: CHMP1A was added to Arthrogryposis. Sources: Expert Review Red Mode of inheritance for gene: CHMP1A was set to |
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| Arthrogryposis v2.62 | ERCC1 |
Rebecca Foulger gene: ERCC1 was added gene: ERCC1 was added to Arthrogryposis. Sources: Literature,Expert Review Red Mode of inheritance for gene: ERCC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERCC1 were set to 17273966; 23623389 Phenotypes for gene: ERCC1 were set to Cerebrooculofacioskeletal syndrome 4 |
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| Arthrogryposis v2.62 | CEP55 |
Rebecca Foulger gene: CEP55 was added gene: CEP55 was added to Arthrogryposis. Sources: Literature,Expert Review Red Mode of inheritance for gene: CEP55 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP55 were set to 28264986; 30622327 Phenotypes for gene: CEP55 were set to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly |
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| Arthrogryposis v2.62 | DHCR24 |
Rebecca Foulger gene: DHCR24 was added gene: DHCR24 was added to Arthrogryposis. Sources: Literature,Expert Review Green Mode of inheritance for gene: DHCR24 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DHCR24 were set to 21559050; 21671375; 12457401; 29175559 Phenotypes for gene: DHCR24 were set to dermosterolsis |
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| Arthrogryposis v2.62 | ALG3 |
Rebecca Foulger gene: ALG3 was added gene: ALG3 was added to Arthrogryposis. Sources: Literature,Expert Review Green Mode of inheritance for gene: ALG3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALG3 were set to 26453362; 28742265; 16006436 Phenotypes for gene: ALG3 were set to Congenital disorder of glycosylation, type Id |
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| Arthrogryposis v2.62 | ZNF335 |
Rebecca Foulger gene: ZNF335 was added gene: ZNF335 was added to Arthrogryposis. Sources: Literature,Expert Review Red Mode of inheritance for gene: ZNF335 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZNF335 were set to 23178126 Phenotypes for gene: ZNF335 were set to Microcephaly 10, primary, autosomal recessive |
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| Arthrogryposis v2.62 | SLC6A9 |
Rebecca Foulger gene: SLC6A9 was added gene: SLC6A9 was added to Arthrogryposis. Sources: Literature,Other,Expert Review Green Mode of inheritance for gene: SLC6A9 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC6A9 were set to Glycine encephalopathy with normal serum glycine, 617301; Glycine Encephalopathy with Arthrogryposis |
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| Arthrogryposis v2.62 | MAGEL2 |
Rebecca Foulger gene: MAGEL2 was added gene: MAGEL2 was added to Arthrogryposis. Sources: Literature,Other,Expert Review Green Mode of inheritance for gene: MAGEL2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Phenotypes for gene: MAGEL2 were set to Schaaf-Yang syndrome, 615547; ARTHROGRYPOSIS MULTIPLEX CONGENITA |
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| Limb disorders v1.127 | LMBR1 |
Eleanor Williams changed review comment from: Variants within the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene are thought to lead to Preaxial polydactyly. The ZRS is a sonic hedgehog (SHH) regulatory region. It is not thought to affect the expression LMBR1. PMID: 31395945 - Xu et al 2019 - large 4 generation family with isolated preaxial polydactyly. A novel 446T>A ZRS) variant segregates with all PPD I–affected individuals. A knockin mouse with this ZRS variant exhibited PPD I phenotype accompanying ectopic and excess expression of Shh. PMID: 19847792 Wieczorek et al. (2010) - report 2 families (Turkish and Brazilian) with Werner mesomelic syndrome (hypo- or aplasia of the tibiae in addition to the preaxial polydactyly (PPD) of the hands and feet ) with variants in the ZRS region (404G>A and 404G>C). Two other families (families 3 and 4) were reported with duplications (73-kb and 276-kb) affecting the ZRS region. Members of family 3 had Haas type polysyndactyly and family 4 had triphalangeal thumb-polysyndactyly syndrome. PMID: 24965254 Norbnop et al. (2014) - report 2 Thai cases of Werner mesomelic syndrome, one familial with a heterozygous 406A>G variant in the ZRS and one sporadic with a heterozygous 404G>A ZRS mutation. PMID: 24777739 - VanderMeer et al. (2014) - large 5-generation Mexican kindred where affect individuals (with isolated triphalangeal thumb, or preaxial polydactyly with triphalangeal thumbs) were heterozygous for a c.402C->T variant in ZRS region of LMBR1. A more severely affected daughter was homozygous for the same mutation. Summary: > 3 cases where variants in the ZRS are found in patients with polydactyly. In 2 cases duplications covering parts of the ZRS were found in patients with polydactyly. Currently variants in the ZRS would NOT be reported via WGS. Duplications > 10Kb covering the LMBR1 gene would be picked up as the gene is green.; to: Variants within LMBR1 coding sequence: PMID:11090342 - Ianakiev et al - 2001- found a genomic 4- to 6-kb deletion in LMBR1 in 5 unrelated Brazilian families with acheiropody. The deletion led to a trascript lacking exon 4 and introducing a premature stop codon downstream of exon 3. Haplotype analysis confirmed the expectation that a single common ancestral mutation was the cause of all the cases. PMID: 26749485 - Shamseldin et al 2016 - patient with acheiropodia who had a nullizygous deletion of 102 kb spanning LMBR1. The ZRS is a sonic hedgehog (SHH) regulatory region of approx 800bp. It is not thought to affect the expression LMBR1. Variants and duplications affecting the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene: Numerous reports of heterozygous variants in ZRS being associated with preaxial polydactyly/Werner mesomelic syndrome - (PMID: 31395945 - Xu et al 2019 - 1 case, 446T>A ZRS), (PMID: 19847792 Wieczorek et al. (2010) - 2 cases with variants 404G>A and 404G>C ZRS), (PMID: 24965254 Norbnop et al. (2014) - 2 cases, one familial and one sporadic with 406A>G and 404G>A ZRS variants), (PMID: 24777739 - VanderMeer et al. (2014) - 1 case - 5 generation family with a c.402C->T variant (A more severely affected daughter was homozygous for the same mutation)). Other cases listed in OMIM. PMID: 28127823 - Xiang et al 2017 - report 6/102 of patients with preaxial polydactyly type I with variants in a region upstream of the ZRS. Reports of duplications covering parts of the ZRS also being associated with a limb phenotype. PMID: 19847792 - Wieczorek et al. (2010) - report 2 families (families 3 and 4) with duplications (73-kb and 276-kb) affecting the ZRS region. Members of family 3 had Haas type polysyndactyly and family 4 had triphalangeal thumb-polysyndactyly syndrome. PMID: 18178630 - Klopocki et al 2008 - report a large 4-generation pedigree with variable triphalangeal thumb and polysyndactyly, No point mutations found in the LMBR1 gene but array CGH analysis identified a heterozygous 589-kb duplication comprising the ZRS. PMID: 18417549 - Sun et al 2009 - in 6 Han Chinese families with Triphalangeal thumb-polysyndactyly syndrome they identified duplications of ZRS which segregated with the limb phenotypes in all families. PMID: 19291772 - Wu et al 2009 - in a Chinese family with type IV syndactyly and tibial hypoplasia they detected a duplication of between 105 to 115 kb. Summary: > 3 cases where SNVs in the ZRS are found in patients with polydactyly. In >3 cases duplications covering parts of the ZRS were found in patients with a limb phenotype. Currently variants in the ZRS would NOT be reported via WGS. Duplications > 10Kb covering the LMBR1 gene would be picked up as the gene is green. |
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| Paediatric disorders - additional genes v0.42 | PLD1 | Ellen McDonagh Classified gene: PLD1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.42 | PLD1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber, as two families have been reported (see publication). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.42 | PLD1 | Ellen McDonagh Gene: pld1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.41 | GDF1 | Ellen McDonagh Mode of inheritance for gene: GDF1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.40 | GDF1 | Ellen McDonagh Classified gene: GDF1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.40 | GDF1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green. This gene is Green on the Familial non syndromic congenital heart disease (panel 212, Version 1.49). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.40 | GDF1 | Ellen McDonagh Gene: gdf1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1115 | KCNT2 | Ivone Leong Added comment: Comment on mode of pathogenicity: Variants have gain-of-function effect. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1115 | KCNT2 | Ivone Leong Mode of pathogenicity for gene: KCNT2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.40 | GDF1 | Ellen McDonagh Classified gene: GDF1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.40 | GDF1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green. This gene is Green on the Familial non syndromic congenital heart disease (panel 212, Version 1.49). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.40 | GDF1 | Ellen McDonagh Gene: gdf1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.39 | MYH7 | Ellen McDonagh Added comment: Comment on mode of inheritance: Awaiting confirmation that this gene should be 'both' or monoallelic as mode of inheritance. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.39 | MYH7 | Ellen McDonagh Mode of inheritance for gene: MYH7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.38 | MYH7 | Ellen McDonagh Classified gene: MYH7 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.38 | MYH7 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green, as this gene is Green on multiple version 1+ cardio panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.38 | MYH7 | Ellen McDonagh Gene: myh7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.37 | CFAP53 | Ellen McDonagh Marked gene: CFAP53 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.37 | CFAP53 | Ellen McDonagh Gene: cfap53 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.37 | CFAP53 | Ellen McDonagh Classified gene: CFAP53 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.37 | CFAP53 | Ellen McDonagh Added comment: Comment on list classification: This gene is Green on the Familial non syndromic congenital heart disease (panel 212 version 1.49). Promoted from Red to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.37 | CFAP53 | Ellen McDonagh Gene: cfap53 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.36 | ACTC1 | Ellen McDonagh Classified gene: ACTC1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.36 | ACTC1 | Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green as this gene is on multiple cardio version 1+ panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.36 | ACTC1 | Ellen McDonagh Gene: actc1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | ACTC1 | Ellen McDonagh Marked gene: ACTC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | ACTC1 | Ellen McDonagh Gene: actc1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1114 | KCNT2 | Ivone Leong Phenotypes for gene: KCNT2 were changed from ?Epileptic encephalopathy, early infantile 57, MIM 617771 to ?Epileptic encephalopathy, early infantile 57, 617771 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | DNAH5 | Ellen McDonagh reviewed gene: DNAH5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 3, with or without situs inversus ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | CRELD1 | Ellen McDonagh reviewed gene: CRELD1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Atrioventricular septal defect, partial, with heterotaxy syndrome, Atrioventricular septal defect, susceptibility to, 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | ZFPM2 | Ellen McDonagh reviewed gene: ZFPM2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Tetralogy of Fallot; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | TLL1 | Ellen McDonagh reviewed gene: TLL1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Atrial septal defect 6; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | PRDM6 | Ellen McDonagh reviewed gene: PRDM6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Patent ductus arteriosus 3; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | NKX2-6 | Ellen McDonagh reviewed gene: NKX2-6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Conotruncal heart malformations, Persistent truncus arteriosus; Mode of inheritance: Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | GDF1 | Ellen McDonagh reviewed gene: GDF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital heart defects, multiple types, 6, Right atrial isomerism (Ivemark) ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | FOXH1 | Ellen McDonagh reviewed gene: FOXH1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | DNAI1 | Ellen McDonagh reviewed gene: DNAI1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 1, with or without situs inversus ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | DNAH11 | Ellen McDonagh reviewed gene: DNAH11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 7, with or without situs inversus ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | STK4 | Ellen McDonagh reviewed gene: STK4: Rating: AMBER; Mode of pathogenicity: ; Publications: 22294732, 22174160; Phenotypes: T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | PLD1 | Ellen McDonagh reviewed gene: PLD1: Rating: AMBER; Mode of pathogenicity: ; Publications: 27799408; Phenotypes: Cardiac valvular defect, developmental; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | MYH7 | Ellen McDonagh reviewed gene: MYH7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cardiomyopathy, dilated, 1S, Cardiomyopathy, hypertrophic, 1, Laing distal myopathy, Left ventricular noncompaction 5, Myopathy, myosin storage, autosomal dominant, Myopathy, myosin storage, autosomal recessive, Scapuloperoneal syndrome, myopathic type ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | GATA5 | Ellen McDonagh reviewed gene: GATA5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital heart defects, multiple types, 5; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | CITED2 | Ellen McDonagh reviewed gene: CITED2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Atrial septal defect 8, Ventricular septal defect 2 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | CFAP53 | Ellen McDonagh reviewed gene: CFAP53: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Heterotaxy, visceral, 6, autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.35 | ACTC1 | Ellen McDonagh reviewed gene: ACTC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Atrial septal defect 5, Cardiomyopathy, dilated, 1R, Cardiomyopathy, hypertrophic, 11, Left ventricular noncompaction 4; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1113 | TMX2 | Ivone Leong Classified gene: TMX2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1113 | TMX2 | Ivone Leong Added comment: Comment on list classification: New gene submitted by expert reviewer. Based on the submitted evidence the gene has been given an Amber rating until further evidence is available to promote it to Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1113 | TMX2 | Ivone Leong Gene: tmx2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1112 | CNOT2 | Ivone Leong Classified gene: CNOT2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1112 | CNOT2 | Ivone Leong Added comment: Comment on list classification: New gene added by expert reviewer. There is enough evidence to promote this gene to Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1112 | CNOT2 | Ivone Leong Gene: cnot2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1111 | CNOT2 | Ivone Leong Phenotypes for gene: CNOT2 were changed from Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies, MIM 618608 to Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies, 618608 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.61 | STIM1 | Rebecca Foulger Classified gene: STIM1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.61 | STIM1 | Rebecca Foulger Gene: stim1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.60 | STIM1 | Rebecca Foulger commented on gene: STIM1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.60 | ORAI1 | Rebecca Foulger Mode of inheritance for gene: ORAI1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.59 | ORAI1 | Rebecca Foulger Classified gene: ORAI1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.59 | ORAI1 | Rebecca Foulger Gene: orai1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.58 | ORAI1 | Rebecca Foulger commented on gene: ORAI1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.58 | STAC3 | Rebecca Foulger commented on gene: STAC3: Although the variants were originally only reported from the same population (Lumbee Indian tribe), PMID:28777491 (Telegrafi et al., 2017) report the W284S homozygous variant in a child born of consanguineous parents from Qatar, and in a compound het state in 2 siblings from Puerto Rico. This demonstrates that this variant is not restricted to the Native American population and I have therefore removed the 'founder-effect' tag. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.58 | STAC3 | Rebecca Foulger Tag founder-effect was removed from gene: STAC3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.58 | STAC3 | Rebecca Foulger Classified gene: STAC3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.58 | STAC3 | Rebecca Foulger Gene: stac3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.57 | STAC3 | Rebecca Foulger commented on gene: STAC3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.57 | DPAGT1 | Rebecca Foulger changed review comment from: Comment on list classification: Updated DPAGT1 from Red to Green on advice from Zerin Hyder (Genomics England Clinical Team), and additional evidence from PMID: 26033833 and PMID:30653653.; to: Comment on list classification: Updated DPAGT1 from Red to Green on advice from Zerin Hyder (Genomics England Clinical Team), and additional evidence from PMID: 26033833 and PMID:30653653. DPAGT1 is also Green on the 'Neuromuscular arthrogryposis' v0.21 panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.57 | LMNA | Rebecca Foulger Classified gene: LMNA as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.57 | LMNA | Rebecca Foulger Added comment: Comment on list classification: Kept rating of LMNA as Red based on advice from Zerin Hyder (Genomics England Clinical Team). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.57 | LMNA | Rebecca Foulger Gene: lmna has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.353 | SMN1 | Rebecca Foulger Publications for gene: SMN1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.56 | DPAGT1 | Rebecca Foulger Classified gene: DPAGT1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.56 | DPAGT1 | Rebecca Foulger Added comment: Comment on list classification: Updated DPAGT1 from Red to Green on advice from Zerin Hyder (Genomics England Clinical Team), and additional evidence from PMID: 26033833 and PMID:30653653. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.56 | DPAGT1 | Rebecca Foulger Gene: dpagt1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.55 | DPAGT1 | Rebecca Foulger Phenotypes for gene: DPAGT1 were changed from Congenital disorder of glycosylation, type Ij, 608093Myasthenic syndrome, congenital, with tubular aggregates 2, 614750 to Congenital disorder of glycosylation, type Ij, 608093; Myasthenic syndrome, congenital, with tubular aggregates 2, 614750 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.54 | DPAGT1 | Rebecca Foulger Publications for gene: DPAGT1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.53 | LMNA | Rebecca Foulger Publications for gene: LMNA were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v0.23 | KIF5A | Louise Daugherty edited their review of gene: KIF5A: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.52 | TTN | Rebecca Foulger Classified gene: TTN as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.52 | TTN | Rebecca Foulger Gene: ttn has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.51 | TTN | Rebecca Foulger Mode of inheritance for gene: TTN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.50 | TTN | Rebecca Foulger Added comment: Comment on mode of inheritance: Changed MOI from 'BOTH monoallelic and biallelic' to 'BIALLELIC' to match MOI on 'Neuromuscular arthrogryposis' panel V0.21 and review on DDG2P panel by Lucy Raymond. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.50 | TTN | Rebecca Foulger Mode of inheritance for gene: TTN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.49 | TTN | Rebecca Foulger Phenotypes for gene: TTN were changed from Hereditary Myopathy with Early Respiratory Failure; Cardiomyopathy, familial hypertrophic, 9, 613765; Hereditary Myopathy with Early Respiratory Failure (dominant); Udd Distal Myopathy (Dominant); Salih Myopathy (recessive); core myopathy with heart disease to Congenital titinopathy with arthrogryposis; Hereditary Myopathy with Early Respiratory Failure; Cardiomyopathy, familial hypertrophic, 9, 613765; Hereditary Myopathy with Early Respiratory Failure (dominant); Udd Distal Myopathy (Dominant); Salih Myopathy (recessive); core myopathy with heart disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v0.23 | KIF5A | Louise Daugherty Phenotypes for gene: KIF5A were changed from Hereditaryspastic paraplegia to Hereditary spastic paraplegia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.48 | TTN | Rebecca Foulger Publications for gene: TTN were set to 24105469 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v0.22 | KIF5A | Louise Daugherty Classified gene: KIF5A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v0.22 | KIF5A | Louise Daugherty Added comment: Comment on list classification: Downgraded gene from Green to Amber from expert review David Lynch. This approach was also agreed in principle with the Genomic England clinical team (25th November 2019), the change will be flagged up in the sign-off email to the test group for this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v0.22 | KIF5A | Louise Daugherty Gene: kif5a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.47 | TTN | Rebecca Foulger commented on gene: TTN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v0.34 | DNAH5 |
Ellen McDonagh gene: DNAH5 was added gene: DNAH5 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: DNAH5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAH5 were set to Ciliary dyskinesia, primary, 3, with or without situs inversus |
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| Paediatric disorders - additional genes v0.34 | CRELD1 |
Ellen McDonagh gene: CRELD1 was added gene: CRELD1 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: CRELD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: CRELD1 were set to Atrioventricular septal defect, partial, with heterotaxy syndrome; Atrioventricular septal defect, susceptibility to, 2 |
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| Paediatric disorders - additional genes v0.34 | ZFPM2 |
Ellen McDonagh gene: ZFPM2 was added gene: ZFPM2 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: ZFPM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ZFPM2 were set to Tetralogy of Fallot |
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| Paediatric disorders - additional genes v0.34 | TLL1 |
Ellen McDonagh gene: TLL1 was added gene: TLL1 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: TLL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: TLL1 were set to Atrial septal defect 6 |
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| Paediatric disorders - additional genes v0.34 | PRDM6 |
Ellen McDonagh gene: PRDM6 was added gene: PRDM6 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: PRDM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: PRDM6 were set to Patent ductus arteriosus 3 |
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| Paediatric disorders - additional genes v0.34 | NKX2-6 |
Ellen McDonagh gene: NKX2-6 was added gene: NKX2-6 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: NKX2-6 was set to Unknown Phenotypes for gene: NKX2-6 were set to Conotruncal heart malformations; Persistent truncus arteriosus |
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| Paediatric disorders - additional genes v0.34 | GDF1 |
Ellen McDonagh gene: GDF1 was added gene: GDF1 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: GDF1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: GDF1 were set to Right atrial isomerism (Ivemark); Congenital heart defects, multiple types, 6 |
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| Paediatric disorders - additional genes v0.34 | FOXH1 |
Ellen McDonagh gene: FOXH1 was added gene: FOXH1 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: FOXH1 was set to Unknown |
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| Paediatric disorders - additional genes v0.34 | DNAI1 |
Ellen McDonagh gene: DNAI1 was added gene: DNAI1 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: DNAI1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAI1 were set to Ciliary dyskinesia, primary, 1, with or without situs inversus |
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| Paediatric disorders - additional genes v0.34 | DNAH11 |
Ellen McDonagh gene: DNAH11 was added gene: DNAH11 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: DNAH11 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DNAH11 were set to Ciliary dyskinesia, primary, 7, with or without situs inversus |
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| Paediatric disorders - additional genes v0.34 | STK4 |
Ellen McDonagh gene: STK4 was added gene: STK4 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: STK4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STK4 were set to 22294732; 22174160 Phenotypes for gene: STK4 were set to T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations |
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| Paediatric disorders - additional genes v0.34 | PLD1 |
Ellen McDonagh gene: PLD1 was added gene: PLD1 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: PLD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLD1 were set to 27799408 Phenotypes for gene: PLD1 were set to Cardiac valvular defect, developmental |
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| Paediatric disorders - additional genes v0.34 | MYH7 |
Ellen McDonagh gene: MYH7 was added gene: MYH7 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: MYH7 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: MYH7 were set to Cardiomyopathy, dilated, 1S; Left ventricular noncompaction 5; Cardiomyopathy, hypertrophic, 1; Myopathy, myosin storage, autosomal recessive; Myopathy, myosin storage, autosomal dominant; Scapuloperoneal syndrome, myopathic type; Laing distal myopathy |
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| Paediatric disorders - additional genes v0.34 | GATA5 |
Ellen McDonagh gene: GATA5 was added gene: GATA5 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: GATA5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: GATA5 were set to Congenital heart defects, multiple types, 5 |
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| Paediatric disorders - additional genes v0.34 | CITED2 |
Ellen McDonagh gene: CITED2 was added gene: CITED2 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: CITED2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: CITED2 were set to Atrial septal defect 8; Ventricular septal defect 2 |
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| Paediatric disorders - additional genes v0.34 | CFAP53 |
Ellen McDonagh gene: CFAP53 was added gene: CFAP53 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: CFAP53 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CFAP53 were set to Heterotaxy, visceral, 6, autosomal recessive |
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| Paediatric disorders - additional genes v0.34 | ACTC1 |
Ellen McDonagh gene: ACTC1 was added gene: ACTC1 was added to Paediatric disorders - additional genes. Sources: South West GLH Mode of inheritance for gene: ACTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ACTC1 were set to Atrial septal defect 5; Cardiomyopathy, hypertrophic, 11; Cardiomyopathy, dilated, 1R; Left ventricular noncompaction 4 |
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| DDG2P v1.154 | SIM1 | Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from 'both MONOALLELIC and BIALLELIC' to just 'MONOALLELIC' to match the Monoallelic MOI of SIM1 on the 'Severe early-onset obesity' panel v2.0. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.154 | SIM1 | Rebecca Foulger Mode of inheritance for gene: SIM1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.127 | LMBR1 | Eleanor Williams commented on gene: LMBR1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1110 | DMXL2 | Ivone Leong Classified gene: DMXL2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1110 | DMXL2 | Ivone Leong Added comment: Comment on list classification: Promoted from Red to Green based on expert reviewer's comments/evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1110 | DMXL2 | Ivone Leong Gene: dmxl2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1109 | DMXL2 | Ivone Leong Phenotypes for gene: DMXL2 were changed from Sensorineural Hearing Loss; ORPHA90636; OMIM:612186 to Sensorineural Hearing Loss; ORPHA90636; Epileptic encephalopathy, early infantile, 81, 618663; ?Polyendocrine-polyneuropathy syndrome, 616113 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1108 | DMXL2 | Ivone Leong Publications for gene: DMXL2 were set to 25248098 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clefting v1.60 | ARHGAP29 | Catherine Snow Classified gene: ARHGAP29 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clefting v1.60 | ARHGAP29 | Catherine Snow Gene: arhgap29 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clefting v1.59 | ARHGAP29 | Catherine Snow reviewed gene: ARHGAP29: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.153 | GJB2 | Rebecca Foulger Classified gene: GJB2 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.153 | GJB2 | Rebecca Foulger Added comment: Comment on list classification: Removed GJB2 from the DDG2P panel, because all gene:disease associations (5 confirmed diseases) have been removed from Gene2Phenotype in October 2019. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.153 | GJB2 | Rebecca Foulger Gene: gjb2 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.153 | GJB2 | Rebecca Foulger Classified gene: GJB2 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.153 | GJB2 | Rebecca Foulger Added comment: Comment on list classification: Removed GJB2 from the DDG2P panel, because all gene:disease associations (5 confirmed diseases) have been removed from Gene2Phenotype in October 2019. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.153 | GJB2 | Rebecca Foulger Gene: gjb2 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | WDR4 | Rebecca Foulger reviewed gene: WDR4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | WDFY3 | Rebecca Foulger reviewed gene: WDFY3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | TPRKB | Rebecca Foulger reviewed gene: TPRKB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | TP53RK | Rebecca Foulger reviewed gene: TP53RK: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | SMPD4 | Rebecca Foulger reviewed gene: SMPD4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | NUP133 | Rebecca Foulger reviewed gene: NUP133: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | NPM1 | Rebecca Foulger reviewed gene: NPM1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | MYRF | Rebecca Foulger reviewed gene: MYRF: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | METTL5 | Rebecca Foulger reviewed gene: METTL5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | MESD | Rebecca Foulger reviewed gene: MESD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | MAB21L1 | Rebecca Foulger reviewed gene: MAB21L1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | LINGO1 | Rebecca Foulger reviewed gene: LINGO1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | LAGE3 | Rebecca Foulger reviewed gene: LAGE3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | KIF14 | Rebecca Foulger reviewed gene: KIF14: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | KCNT2 | Rebecca Foulger reviewed gene: KCNT2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | KCNA4 | Rebecca Foulger reviewed gene: KCNA4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | GRIA4 | Rebecca Foulger reviewed gene: GRIA4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | DEGS1 | Rebecca Foulger reviewed gene: DEGS1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | DACT1 | Rebecca Foulger reviewed gene: DACT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | CDH2 | Rebecca Foulger reviewed gene: CDH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.152 | APC2 | Rebecca Foulger reviewed gene: APC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.151 | WDR4 |
Rebecca Foulger gene: WDR4 was added gene: WDR4 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Red Mode of inheritance for gene: WDR4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WDR4 were set to 30079490 Phenotypes for gene: WDR4 were set to GALLOWAY-MOWAT SYNDROME 6, 618347 |
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| DDG2P v1.151 | WDFY3 |
Rebecca Foulger gene: WDFY3 was added gene: WDFY3 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: WDFY3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: WDFY3 were set to 31327001 Phenotypes for gene: WDFY3 were set to Primary Microcephaly or macrocephaly with developmental delay |
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| DDG2P v1.151 | TPRKB |
Rebecca Foulger gene: TPRKB was added gene: TPRKB was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Red Mode of inheritance for gene: TPRKB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TPRKB were set to 28805828 Phenotypes for gene: TPRKB were set to GALLOWAY-MOWAT SYNDROME 5, 617731 Mode of pathogenicity for gene: TPRKB was set to Other - please provide details in the comments |
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| DDG2P v1.151 | TP53RK |
Rebecca Foulger gene: TP53RK was added gene: TP53RK was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: TP53RK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TP53RK were set to 30053862; 28805828 Phenotypes for gene: TP53RK were set to GALLOWAY-MOWAT SYNDROME 4, 617730 |
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| DDG2P v1.151 | SMPD4 |
Rebecca Foulger gene: SMPD4 was added gene: SMPD4 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: SMPD4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMPD4 were set to 31495489 Phenotypes for gene: SMPD4 were set to Developmental Disorder with Microcephaly and Congenital Arthrogryposis |
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| DDG2P v1.151 | NUP133 |
Rebecca Foulger gene: NUP133 was added gene: NUP133 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: NUP133 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP133 were set to 30427554 Phenotypes for gene: NUP133 were set to GALLOWAY-MOWAT SYNDROME 8, 618349 |
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| DDG2P v1.151 | NPM1 |
Rebecca Foulger gene: NPM1 was added gene: NPM1 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: NPM1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NPM1 were set to 31570891 Phenotypes for gene: NPM1 were set to Dyskeratosis Congenita Mode of pathogenicity for gene: NPM1 was set to Other - please provide details in the comments |
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| DDG2P v1.151 | MYRF |
Rebecca Foulger gene: MYRF was added gene: MYRF was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: MYRF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MYRF were set to 31069960; 29446546; 30532227; 30070761 Phenotypes for gene: MYRF were set to Pulmonary artery and lung hypoplasia, agonadism, omphalocele, diaphragmatic defects, hypoplastic left heart and scimitar syndrome |
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| DDG2P v1.151 | METTL5 |
Rebecca Foulger gene: METTL5 was added gene: METTL5 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: METTL5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: METTL5 were set to 31564433 Phenotypes for gene: METTL5 were set to Autosomal-Recessive Intellectual Disability and Microcephaly |
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| DDG2P v1.151 | MESD |
Rebecca Foulger gene: MESD was added gene: MESD was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MESD were set to 31564437 Phenotypes for gene: MESD were set to OSTEOGENESIS IMPERFECTA |
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| DDG2P v1.151 | MAB21L1 |
Rebecca Foulger gene: MAB21L1 was added gene: MAB21L1 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: MAB21L1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAB21L1 were set to 27103078; 30487245 Phenotypes for gene: MAB21L1 were set to Cerebello-Oculo-Facio-Genital syndrome |
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| DDG2P v1.151 | LINGO1 |
Rebecca Foulger gene: LINGO1 was added gene: LINGO1 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: LINGO1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LINGO1 were set to 28837161 Phenotypes for gene: LINGO1 were set to LINGO1 related intellectual disability with microcephaly, speech and motor delay |
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| DDG2P v1.151 | LAGE3 |
Rebecca Foulger gene: LAGE3 was added gene: LAGE3 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Red Mode of inheritance for gene: LAGE3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: LAGE3 were set to 28805828 Phenotypes for gene: LAGE3 were set to GALLOWAY-MOWAT SYNDROME 2, 301006 Mode of pathogenicity for gene: LAGE3 was set to Other - please provide details in the comments |
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| DDG2P v1.151 | KIF14 |
Rebecca Foulger gene: KIF14 was added gene: KIF14 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: KIF14 was set to Publications for gene: KIF14 were set to 24128419; 28892560 Phenotypes for gene: KIF14 were set to Severe microcephaly and short stature |
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| DDG2P v1.151 | KCNT2 |
Rebecca Foulger gene: KCNT2 was added gene: KCNT2 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Red Mode of inheritance for gene: KCNT2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KCNT2 were set to 29740868 Phenotypes for gene: KCNT2 were set to Developmental and infantile epileptic encephalopathy Mode of pathogenicity for gene: KCNT2 was set to Other - please provide details in the comments |
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| DDG2P v1.151 | KCNA4 |
Rebecca Foulger gene: KCNA4 was added gene: KCNA4 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Red Mode of inheritance for gene: KCNA4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: KCNA4 were set to KCN4 related abnormal striatum, congenital cataract and intellectual disability. Mode of pathogenicity for gene: KCNA4 was set to Other - please provide details in the comments |
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| DDG2P v1.151 | GRIA4 |
Rebecca Foulger gene: GRIA4 was added gene: GRIA4 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Red Mode of inheritance for gene: GRIA4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: GRIA4 were set to 29220673 Phenotypes for gene: GRIA4 were set to NEURODEVELOPMENTAL DISORDER WITH OR WITHOUT SEIZURES AND GAIT ABNORMALITIES, 617864 Mode of pathogenicity for gene: GRIA4 was set to Other - please provide details in the comments |
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| DDG2P v1.151 | DEGS1 |
Rebecca Foulger gene: DEGS1 was added gene: DEGS1 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Green Mode of inheritance for gene: DEGS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DEGS1 were set to 31186544; 30620337 Phenotypes for gene: DEGS1 were set to LEUKODYSTROPHY, HYPOMYELINATING, 18, 618404 |
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| DDG2P v1.151 | DACT1 |
Rebecca Foulger gene: DACT1 was added gene: DACT1 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Red Mode of inheritance for gene: DACT1 was set to Publications for gene: DACT1 were set to 28054444; 22610794 Phenotypes for gene: DACT1 were set to Multiple malformations of neural tube, ear, genitourinary and gastrointestinal systems |
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| DDG2P v1.151 | CDH2 |
Rebecca Foulger gene: CDH2 was added gene: CDH2 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: CDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CDH2 were set to 31650526; 31585109 Phenotypes for gene: CDH2 were set to Syndromic Neurodevelopmental Disorder with Corpus Collosum, Axon, Cardiac, Ocular, and Genital Defects Mode of pathogenicity for gene: CDH2 was set to Other - please provide details in the comments |
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| DDG2P v1.151 | APC2 |
Rebecca Foulger gene: APC2 was added gene: APC2 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: APC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: APC2 were set to 31585108 Phenotypes for gene: APC2 were set to Lissencephaly, Subcortical Heterotopia, and Global Developmental Delay |
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| Paediatric or syndromic cardiomyopathy v0.13 | MLYCD | James Eden changed review comment from: Cardiomyopathy is one of the main presenting features of this condition along with development delay, hypotonia, seizures, diarrhoea, vomiting hypoglycemia (Genetics Home Reference).; to: Cardiomyopathy is one of the main presenting features of this condition along with development delay, hypotonia, seizures, diarrhoea, vomiting and hypoglycemia (Genetics Home Reference). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | MLYCD | James Eden changed review comment from: Cardiomyopathy is one of main presenting features of this condition.; to: Cardiomyopathy is one of the main presenting features of this condition along with development delay, hypotonia, seizures, diarrhoea, vomiting hypoglycemia (Genetics Home Reference). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | MLYCD | James Eden reviewed gene: MLYCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 7609455, 9177981, 12955715; Phenotypes: Malonyl-CoA decarboxylase deficiency, 248360; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | LRPPRC | James Eden reviewed gene: LRPPRC: Rating: AMBER; Mode of pathogenicity: None; Publications: 12529507, 26510951, 22045337, 24399447; Phenotypes: Leigh syndrome, French-Canadian type, 220111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | ISCA-37431-Loss | James Eden reviewed Region: ISCA-37431-Loss: Rating: AMBER; Mode of pathogenicity: None; Publications: 14729829, 12180143; Phenotypes: Chromosome 17q11.2 deletion syndrome 1.4Mb, 613675; Mode of inheritance: Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | IDUA | James Eden reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: 9686810; Phenotypes: Mucopolysaccharidosis (MPS) type I, 607014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | HGSNAT | James Eden changed review comment from: Gene is associated with mucopolysaccharidosis MPS type III-C (Sanfilippo C). Cardiomyopathy has been described on one occasion as a presenting feature (PMID 21048366).; to: Gene is associated with mucopolysaccharidosis MPS type III-C (Sanfilippo C). Cardiomyopathy has been described on one occasion as a presenting feature but in a 39 year old (PMID 21048366). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric or syndromic cardiomyopathy v0.13 | HGSNAT | James Eden reviewed gene: HGSNAT: Rating: RED; Mode of pathogenicity: None; Publications: 21048366; Phenotypes: Mucopolysaccharidosis type IIIC (Sanfilippo C), 252930, Retinitis pigmentosa 73, 616544; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.150 | NUP107 | Rebecca Foulger Phenotypes for gene: NUP107 were changed from EARLY-CHILDHOOD-ONSET STEROID-RESISTANT NEPHROTIC SYNDROME to GALLOWAY-MOWAT SYNDROME 7, 618348; EARLY-CHILDHOOD-ONSET STEROID-RESISTANT NEPHROTIC SYNDROME | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.149 | NUP107 | Rebecca Foulger Publications for gene: NUP107 were set to 26411495 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.148 | NUP107 | Rebecca Foulger commented on gene: NUP107: New gene:disorder association added to DDG2P October 2019: GALLOWAY-MOWAT SYNDROME 7, 618348. G2P Allelic requirement: biallelic. G2P Mutation consequence: loss of function. G2P Disease confidence rating: possible. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.127 | SMAD6 | Eleanor Williams Classified gene: SMAD6 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.127 | SMAD6 |
Eleanor Williams Added comment: Comment on list classification: Promoting from red to green. Notes from Genomics England clinical team - Sufficient cases, scope of panel includes radial anomalies therefore potentially informative for some patients. Note reduced penetrance. |
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| Limb disorders v1.127 | SMAD6 | Eleanor Williams Gene: smad6 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.126 | FAM92A |
Eleanor Williams changed review comment from: Provisionally associated with ?Polydactyly, postaxial, type A9 (#618219) in OMIM. PMID: 30395363 - Schrauwen et al. 2018 - 1 case. They report a consanguineous Pakistani family with 3 children with autosomal recessive nonsyndromic postaxial polydactyly type A. By exome sequencing they identified a homozygous nonsense variant (NM_001283034.1:c.478C>T, NP_001269963.1: p.[Arg160*]) in the FAM92A gene in one child. Sanger sequencing confirmed that this variant segregates with PAPA. The c.478C>T variant (rs368652620) was observed in the gnomAD database with a very low MAF in the exome data (all populations MAF=2.04×10−5, South East Asians MAF=6.55×10−5 and no homozygous individuals observed and ) and was also not present in Sanger sequence data from 186 in-house control Pakistani DNAs. It is predicted to be targeted by the classical nonsense-mediated decay pathway. In mouse studies, FAM92A is expressed in the developing mouse limb and Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri.; to: Provisionally associated with ?Polydactyly, postaxial, type A9 (#618219) in OMIM. PMID: 30395363 - Schrauwen et al. 2018 - 1 case. They report a consanguineous Pakistani family with 3 children with autosomal recessive nonsyndromic postaxial polydactyly type A with a homozygous nonsense variant (NM_001283034.1:c.478C>T, NP_001269963.1: p.[Arg160*]) in the FAM92A gene. It was confirmed that this variant segregates with PAPA. The c.478C>T variant (rs368652620) was observed in the gnomAD database with a very low MAF in the exome data (all populations MAF=2.04×10−5, South East Asians MAF=6.55×10−5 and no homozygous individuals observed and ) and was also not present in Sanger sequence data from 186 in-house control Pakistani DNAs. In mouse studies, FAM92A is expressed in the developing mouse limb and Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri. |
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| Limb disorders v1.126 | FAM92A |
Eleanor Williams changed review comment from: Provisionally associated with ?Polydactyly, postaxial, type A9 (#618219) in OMIM. PMID: 30395363 - Schrauwen et al. 2018 - 1 case. They report a consanguineous Pakistani family with 3 children with autosomal recessive nonsyndromic postaxial polydactyly type A. Blood was taken from 3 affected and 3 non-affected idividuals. DNA from one child was used for exome sequencing and revealed a homozygous nonsense variant (NM_001283034.1:c.478C>T, NP_001269963.1: p.[Arg160*]) in the FAM92A gene. Sanger sequencing confirmed that this variant segregates with PAPA. The c.478C>T variant (rs368652620) was observed in the gnomAD database with a very low MAF in the exome data (all populations MAF=2.04×10−5, South East Asians MAF=6.55×10−5 and no homozygous individuals observed and ) and was also not present in Sanger sequence data from 186 in-house control Pakistani DNAs. It is predicted to be targeted by the classical nonsense-mediated decay pathway. In mouse studies, FAM92A is expressed in the developing mouse limb and Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri. we performed genomewide genotyping, linkage analysis, and exome and Sanger sequencing. Exome sequencing revealed a homozygous nonsense variant (c.478C>T, p.[Arg160*]) in the FAM92A gene within the mapped region on 8q21.13-q24.12 that segregated with the PAPA phenotype. In 3 Pakistani brothers with postaxial polydactyly type A9 (PAPA9; 618219), identified homozygosity for a nonsense mutation in the FAM92A gene (R160X; 617273.0001) that segregated with disease and was not found in 186 Pakistani controls. ▼ Animal Model Schrauwen et al. (2018) generated Fam92a -/- mice and observed extra bone growth or exostosis on the deltoid tuberosity of the humerus, consistent with tendon calcification. Abnormal digit morphology was significantly enriched in the mutant mice compared to controls, and included polysyndactyly and osteomas; to: Provisionally associated with ?Polydactyly, postaxial, type A9 (#618219) in OMIM. PMID: 30395363 - Schrauwen et al. 2018 - 1 case. They report a consanguineous Pakistani family with 3 children with autosomal recessive nonsyndromic postaxial polydactyly type A. By exome sequencing they identified a homozygous nonsense variant (NM_001283034.1:c.478C>T, NP_001269963.1: p.[Arg160*]) in the FAM92A gene in one child. Sanger sequencing confirmed that this variant segregates with PAPA. The c.478C>T variant (rs368652620) was observed in the gnomAD database with a very low MAF in the exome data (all populations MAF=2.04×10−5, South East Asians MAF=6.55×10−5 and no homozygous individuals observed and ) and was also not present in Sanger sequence data from 186 in-house control Pakistani DNAs. It is predicted to be targeted by the classical nonsense-mediated decay pathway. In mouse studies, FAM92A is expressed in the developing mouse limb and Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri. |
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| Limb disorders v1.126 | POLR1A | Eleanor Williams Classified gene: POLR1A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.126 | POLR1A | Eleanor Williams Added comment: Comment on list classification: 2 cases with a limb phenotype therefore rating amber. Rating agreed with Genomics England clinical team. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.126 | POLR1A | Eleanor Williams Gene: polr1a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.125 | POLR1A | Eleanor Williams Publications for gene: POLR1A were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.124 | POLR1A | Eleanor Williams Phenotypes for gene: POLR1A were changed from to Acrofacial dysostosis, Cincinnati type, 616462 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.123 | GZF1 | Eleanor Williams Classified gene: GZF1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.123 | GZF1 | Eleanor Williams Added comment: Comment on list classification: Keeping red. Genomics England clinical team note this is not a particularly limb-predominant phenotype, and is better suited to the skeletal dysplasia/Stickler syndrome panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.123 | GZF1 | Eleanor Williams Gene: gzf1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.122 | SUFU | Eleanor Williams Classified gene: SUFU as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.122 | SUFU | Eleanor Williams Added comment: Comment on list classification: 3 out of 4 children from 2 families had post-axial polydactyly so rating amber. Rating agreed with Genomics England clinical team. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.122 | SUFU | Eleanor Williams Gene: sufu has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.121 | TRAF7 | Eleanor Williams changed review comment from: Comment on list classification: From Genomics England clinical team - there is evidence of a gene:disease association, however the reported limb differences (distal contractures, altered creases or overlapping digits) do not particularly align with the clinical indication for this panel. One subject in the paper has quite marked radial / ulnar directional deformities of the digits though, therefore amber.; to: Comment on list classification: From Genomics England clinical team - there is evidence of a gene:disease association, however the reported limb differences (distal contractures, altered creases or overlapping digits) do not particularly align with the clinical indication for this panel. One subject in the paper has quite marked radial / ulnar directional deformities of the digits though, therefore amber. Green on Intellectual disability, fetal anomalies, DDG2P panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.121 | TRAF7 | Eleanor Williams Classified gene: TRAF7 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.121 | TRAF7 | Eleanor Williams Added comment: Comment on list classification: From Genomics England clinical team - there is evidence of a gene:disease association, however the reported limb differences (distal contractures, altered creases or overlapping digits) do not particularly align with the clinical indication for this panel. One subject in the paper has quite marked radial / ulnar directional deformities of the digits though, therefore amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.121 | TRAF7 | Eleanor Williams Gene: traf7 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.120 | NXN | Eleanor Williams Tag watchlist tag was added to gene: NXN. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.120 | NXN | Eleanor Williams Classified gene: NXN as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.120 | NXN | Eleanor Williams Added comment: Comment on list classification: Only two unrelated families to date so amber rating - agreed with Genomics England clinical team. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.120 | NXN | Eleanor Williams Gene: nxn has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.119 | NXN | Eleanor Williams Phenotypes for gene: NXN were changed from Robinow syndrome to Robinow syndrome, autosomal recessive 2, 618529 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.118 | NXN | Eleanor Williams commented on gene: NXN: Now associated with Robinow syndrome, autosomal recessive 2 #618529 (AR) in OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.118 | FZD2 | Eleanor Williams Classified gene: FZD2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.118 | FZD2 | Eleanor Williams Added comment: Comment on list classification: 4 families, three with brachydactyly and variable presence of other features (clinodactyly, camptodactyly, broad 1st digits). Genomics England clinical team confirm it is appropriate for the limb disorders panel as well as the skeletal dysplasia panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.118 | FZD2 | Eleanor Williams Gene: fzd2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.117 | ASXL1 | Eleanor Williams Classified gene: ASXL1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.117 | ASXL1 | Eleanor Williams Added comment: Comment on list classification: Severe multisystem presentation but various limb disorders are reported including rhizomelia, abnormal flexion at the elbow and wrist, syndactyly and camptodactyly. Green rating agreed with Genomics England clinical team. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.117 | ASXL1 | Eleanor Williams Gene: asxl1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.116 | PAX3 | Eleanor Williams Classified gene: PAX3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.116 | PAX3 | Eleanor Williams Added comment: Comment on list classification: At least two, possibly three, cases and a mouse model. Rating agreed with Genomics England clinical team. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.116 | PAX3 | Eleanor Williams Gene: pax3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.115 | PAX3 | Eleanor Williams Added comment: Comment on mode of inheritance: Biallelic cases show stronger evidence of limb phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.115 | PAX3 | Eleanor Williams Mode of inheritance for gene: PAX3 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | CCDC114 | Matthew Edwards reviewed gene: CCDC114: Rating: GREEN; Mode of pathogenicity: None; Publications: 23261302, 23261303; Phenotypes: OMIM 615067 Ciliary dyskinesia, primary, 20; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | CCDC103 | Matthew Edwards reviewed gene: CCDC103: Rating: GREEN; Mode of pathogenicity: None; Publications: 22581229, 28790179; Phenotypes: OMIM 614679 Ciliary dyskinesia, primary, 17; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | C11orf70 | Matthew Edwards reviewed gene: C11orf70: Rating: GREEN; Mode of pathogenicity: None; Publications: 29727692, 29727693; Phenotypes: OMIM 618063 Ciliary dyskinesia, primary, 38; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | ARMC4 | Matthew Edwards reviewed gene: ARMC4: Rating: GREEN; Mode of pathogenicity: None; Publications: 23849778, 24203976; Phenotypes: OMIM 615451 Ciliary dyskinesia, primary, 23; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | ACVR2B | Matthew Edwards reviewed gene: ACVR2B: Rating: RED; Mode of pathogenicity: None; Publications: 9916847; Phenotypes: OMIM 613751 Heterotaxy, visceral, 4, autosomal; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | ZIC3 | Matthew Edwards reviewed gene: ZIC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: OMIM 306955 Heterotaxy, visceral, 1, X-linked, Congenital heart defects, nonsyndromic, 1, X-linked; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.114 | EIF4A3 |
Eleanor Williams commented on gene: EIF4A3: PMID: 10594883 - Walter-Nicolet et al 1999 - report a French boy with phenotype similar to Richieri-Costa and Pereira form of acrofacial dysostosis but no genome analysis done. PMID: 29112243 - Bertola et al 2018 - describe 5 (4 Brasilian, one from England, of African ancestry) new individuals with Richieri-Costa-Pereira syndrome, including a patient from England, of African ancestry. The patient from England/Kenya showed limb abnormalities of Hypoplastic hallux and club feet only. Expansions of the repeated motif in the 5′ UTR of EIF4A3 were found in all individuals and ranged from 14 to 16 repeats. |
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| Laterality disorders and isomerism v0.51 | TTC25 | Matthew Edwards reviewed gene: TTC25: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486780; Phenotypes: OMIM 617092 Ciliary dyskinesia, primary, 35; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | SPAG1 | Matthew Edwards reviewed gene: SPAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24055112; Phenotypes: OMIM 615505 Ciliary dyskinesia, primary, 28; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | PIH1D3 | Matthew Edwards reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24421334, 28041644,; Phenotypes: OMIM 300991 Ciliary dyskinesia, primary, 36, X-linked; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | NODAL | Matthew Edwards reviewed gene: NODAL: Rating: GREEN; Mode of pathogenicity: None; Publications: 19064609; Phenotypes: OMIM Heterotaxy, visceral, 5270100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | MMP21 | Matthew Edwards reviewed gene: MMP21: Rating: GREEN; Mode of pathogenicity: None; Publications: 26437028, 26429889; Phenotypes: OMIM Heterotaxy, visceral, 7, autosomal; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | CCDC151 | Matthew Edwards reviewed gene: CCDC151: Rating: GREEN; Mode of pathogenicity: None; Publications: 25192045, 25224326; Phenotypes: OMIM 616037 Ciliary dyskinesia, primary, 30; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | LRRC6 | Matthew Edwards reviewed gene: LRRC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23891469, 23122589; Phenotypes: OMIM 614935 Ciliary dyskinesia, primary, 19; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.114 | EIF4A3 | Eleanor Williams Classified gene: EIF4A3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.114 | EIF4A3 | Eleanor Williams Added comment: Comment on list classification: Relevant phenotype, however potential founder effect in the Brazilian population described to date. Further evidence needed therefore rating amber. Rating agreed with Genomics England clinical team. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.114 | EIF4A3 | Eleanor Williams Gene: eif4a3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | LRRC56 | Matthew Edwards reviewed gene: LRRC56: Rating: GREEN; Mode of pathogenicity: None; Publications: 30388400; Phenotypes: OMIM 618254 Ciliary dyskinesia, primary, 39; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | GDF1 | Matthew Edwards reviewed gene: GDF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20413652, 28991257; Phenotypes: OMIM 208530 Right atrial isomerism; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.113 | CYP26B1 | Eleanor Williams Classified gene: CYP26B1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.113 | CYP26B1 | Eleanor Williams Added comment: Comment on list classification: Two families reported to date, one of which had oligodactyly. Further evidence needed before making green. Rating agreed with Genomics England clinical team. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.113 | CYP26B1 | Eleanor Williams Gene: cyp26b1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.112 | ZSWIM6 |
Eleanor Williams changed review comment from: Comment on list classification: Recurrent missense (R1163W) is associated with acromelic frontonasal dysostosis, where relevant limb features are reported. 4 unrelated cases.; to: Comment on list classification: Recurrent missense (R1163W) is associated with acromelic frontonasal dysostosis, where relevant limb features are reported. 4 unrelated cases. Gene is also on the skeletal ciliopathies panel but including here to avoid missing a potential diagnosis in the Genomic Medicine Service. |
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| Laterality disorders and isomerism v0.51 | DNAL1 | Matthew Edwards reviewed gene: DNAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21496787; Phenotypes: OMIM 614017 Ciliary dyskinesia, primary, 16; Mode of inheritance: None; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.112 | ZSWIM6 | Eleanor Williams Classified gene: ZSWIM6 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.112 | ZSWIM6 | Eleanor Williams Added comment: Comment on list classification: Recurrent missense (R1163W) is associated with acromelic frontonasal dysostosis, where relevant limb features are reported. 4 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.112 | ZSWIM6 | Eleanor Williams Gene: zswim6 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | DNAI2 | Matthew Edwards reviewed gene: DNAI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23261302, 18950741; Phenotypes: OMIM 612444 Ciliary dyskinesia, primary, 9, with or without situs inversus; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | DNAI1 | Matthew Edwards reviewed gene: DNAI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10577904, 11231901; Phenotypes: OMIM 244400 Ciliary dyskinesia, primary, 1, with or without situs inversus; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.111 | EFNB1 | Eleanor Williams Classified gene: EFNB1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.111 | EFNB1 | Eleanor Williams Added comment: Comment on list classification: Clear gene:disease association but relatively minor / non-specific digital features. Rating amber based on advice from Genomics England clinical team. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.111 | EFNB1 | Eleanor Williams Gene: efnb1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | DNAH9 | Matthew Edwards reviewed gene: DNAH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 30471717, 30471718; Phenotypes: OMIM 618300 Ciliary dyskinesia, primary, 40; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.110 | TRIM32 | Eleanor Williams commented on gene: TRIM32 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.110 | IFT74 |
Eleanor Williams gene: IFT74 was added gene: IFT74 was added to Limb disorders. Sources: Expert list Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IFT74 were set to 27486776 Phenotypes for gene: IFT74 were set to ?Bardet-Biedl syndrome 20 617119 Review for gene: IFT74 was set to RED Added comment: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. Adding gene as red as it is red on the GMS Bardet Biedl syndrome panel (v1.0). Only 1 case reported plus animal model. Sources: Expert list |
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| Laterality disorders and isomerism v0.51 | DNAH5 | Matthew Edwards reviewed gene: DNAH5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23261302, 11788826, 11062149; Phenotypes: OMIM 608644 Ciliary dyskinesia, primary, 3, with or without situs inversus; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.109 | CEP290 | Eleanor Williams Classified gene: CEP290 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.109 | CEP290 | Eleanor Williams Added comment: Comment on list classification: Adding gene as red as it is red on the GMS Bardet Biedl syndrome panel (v1.0). The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.109 | CEP290 | Eleanor Williams Gene: cep290 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.108 | CCDC28B |
Eleanor Williams gene: CCDC28B was added gene: CCDC28B was added to Limb disorders. Sources: Literature Mode of inheritance for gene: CCDC28B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CCDC28B were set to 23015189 Phenotypes for gene: CCDC28B were set to {Bardet-Biedl syndrome 1, modifier of}, 209900 Review for gene: CCDC28B was set to RED Added comment: Adding gene as red as it is red on the GMS Bardet Biedl syndrome panel (v1.0). Modifier gene Sources: Literature |
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| Laterality disorders and isomerism v0.51 | DNAH11 | Matthew Edwards reviewed gene: DNAH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 12142464, 22184204, 22102620; Phenotypes: OMIM 611884 Ciliary dyskinesia, primary, 7, with or without situs inversus; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.107 | C8orf37 |
Eleanor Williams gene: C8orf37 was added gene: C8orf37 was added to Limb disorders. Sources: Expert list Mode of inheritance for gene: C8orf37 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C8orf37 were set to 27008867; 26854863 Phenotypes for gene: C8orf37 were set to Bardet-Biedl syndrome 21, 617406 Review for gene: C8orf37 was set to RED Added comment: Adding gene as red as it is red on the GMS Bardet Biedl syndrome panel (v1.0). 2 cases reported. Sources: Expert list |
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| Limb disorders v1.106 | BBIP1 |
Eleanor Williams gene: BBIP1 was added gene: BBIP1 was added to Limb disorders. Sources: Expert list Mode of inheritance for gene: BBIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BBIP1 were set to 24026985 Phenotypes for gene: BBIP1 were set to ?Bardet-Biedl syndrome 18, 615995 Added comment: Adding gene as red as it is red on the GMS Bardet Biedl syndrome panel (v1.0). Only 1 case reported. Sources: Expert list |
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| Laterality disorders and isomerism v0.51 | DNAAF5 | Matthew Edwards reviewed gene: DNAAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23040496, 20350728, 29363216; Phenotypes: OMIM 614874 Ciliary dyskinesia, primary, 18; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.105 | TTC8 | Eleanor Williams Classified gene: TTC8 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.105 | TTC8 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.105 | TTC8 | Eleanor Williams Gene: ttc8 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | DNAAF4 | Matthew Edwards reviewed gene: DNAAF4: Rating: ; Mode of pathogenicity: None; Publications: 23872636; Phenotypes: OMIM 615482 Ciliary dyskinesia, primary, 25; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.104 | WDPCP | Eleanor Williams changed review comment from: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. This gene is amber on the GMS Bardet-Biedl syndrome panel https://panelapp.genomicsengland.co.uk/panels/543/; to: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. This gene is amber on the GMS Bardet-Biedl syndrome panel https://panelapp.genomicsengland.co.uk/panels/543/ v1.0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.104 | IFT27 | Eleanor Williams changed review comment from: This gene is amber on the GMS Bardet Biedl syndrome panel https://panelapp.genomicsengland.co.uk/panels/543/; to: This gene is amber on the GMS Bardet Biedl syndrome panel https://panelapp.genomicsengland.co.uk/panels/543/ v1.0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.104 | IFT27 | Eleanor Williams commented on gene: IFT27 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.104 | WDPCP | Eleanor Williams Classified gene: WDPCP as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.104 | WDPCP | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. This gene is amber on the GMS Bardet-Biedl syndrome panel https://panelapp.genomicsengland.co.uk/panels/543/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.104 | WDPCP | Eleanor Williams Gene: wdpcp has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.103 | WDPCP | Eleanor Williams Phenotypes for gene: WDPCP were changed from ?Congenital heart defects, hamartomas of tongue, and polysyndactyly 217085 to ?Congenital heart defects, hamartomas of tongue, and polysyndactyly 217085; ?Bardet-Biedl syndrome 15, 615992 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | DNAAF3 | Matthew Edwards reviewed gene: DNAAF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22387996; Phenotypes: OMIM 606763 Ciliary dyskinesia, primary, 2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.102 | TTC8 | Eleanor Williams Phenotypes for gene: TTC8 were changed from Polydactyly to Polydactyly; Bardet-Biedl syndrome 8, 615985 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.101 | TTC8 | Eleanor Williams Mode of inheritance for gene: TTC8 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.100 | TMEM67 | Eleanor Williams Classified gene: TMEM67 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.100 | TMEM67 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.100 | TMEM67 | Eleanor Williams Gene: tmem67 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.99 | SDCCAG8 | Eleanor Williams Classified gene: SDCCAG8 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.99 | SDCCAG8 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.99 | SDCCAG8 | Eleanor Williams Gene: sdccag8 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | DNAAF2 | Matthew Edwards reviewed gene: DNAAF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 19052621; Phenotypes: OMIM 612518 Ciliary dyskinesia, primary, 10; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.98 | SDCCAG8 | Eleanor Williams Mode of inheritance for gene: SDCCAG8 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.97 | SDCCAG8 | Eleanor Williams Phenotypes for gene: SDCCAG8 were changed from Polydactyly to Polydactyly; Senior-Loken syndrome 7, 613615; Bardet-Biedl syndrome 16, 615993 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.96 | MKS1 | Eleanor Williams Classified gene: MKS1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.96 | MKS1 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.96 | MKS1 | Eleanor Williams Gene: mks1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.95 | MKS1 | Eleanor Williams Phenotypes for gene: MKS1 were changed from Bardet-Biedl syndrome 13 615990; Meckel syndrome 1 249000; Polydactyly to Bardet-Biedl syndrome 13 615990; Meckel syndrome 1 249000; Joubert syndrome 28, 617121; Polydactyly | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.94 | MKKS | Eleanor Williams Classified gene: MKKS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.94 | MKKS | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.94 | MKKS | Eleanor Williams Gene: mkks has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.93 | MKKS | Eleanor Williams Phenotypes for gene: MKKS were changed from Polydactyly to Polydactyly; Bardet-Biedl syndrome 6, 605231; McKusick-Kaufman syndrome, 236700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.92 | MKKS | Eleanor Williams Mode of inheritance for gene: MKKS was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.91 | LZTFL1 | Eleanor Williams Classified gene: LZTFL1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.91 | LZTFL1 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.91 | LZTFL1 | Eleanor Williams Gene: lztfl1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.90 | BBS9 | Eleanor Williams Classified gene: BBS9 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.90 | BBS9 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.90 | BBS9 | Eleanor Williams Gene: bbs9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.89 | BBS9 | Eleanor Williams Mode of pathogenicity for gene: BBS9 was changed from None to None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.88 | BBS9 | Eleanor Williams Phenotypes for gene: BBS9 were changed from Polydactyly to Polydactyly; Bardet Biedl syndrome 9, 615986 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.87 | BBS9 | Eleanor Williams Mode of inheritance for gene: BBS9 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.86 | BBS7 | Eleanor Williams Classified gene: BBS7 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.86 | BBS7 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.86 | BBS7 | Eleanor Williams Gene: bbs7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.85 | BBS7 | Eleanor Williams Phenotypes for gene: BBS7 were changed from Polydactyly to Polydactyly; Bardet-Biedl syndrome 7, 615984 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.84 | BBS7 | Eleanor Williams Mode of inheritance for gene: BBS7 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | DNAAF1 | Matthew Edwards reviewed gene: DNAAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19944405, 19944400, 18385425; Phenotypes: OMIM 613193 Ciliary dyskinesia, primary, 13; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | CFC1 | Matthew Edwards reviewed gene: CFC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 11062482, 25423076; Phenotypes: OMIM 605376 Heterotaxy, visceral, 2, autosomal; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | CFAP53 | Matthew Edwards reviewed gene: CFAP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 25504577, 22577226, 28621423, 26531781; Phenotypes: OMIM 614779 Heterotaxy, visceral, 6, autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.83 | BBS5 | Eleanor Williams Classified gene: BBS5 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.83 | BBS5 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.83 | BBS5 | Eleanor Williams Gene: bbs5 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.82 | BBS5 | Eleanor Williams Phenotypes for gene: BBS5 were changed from Polydactyly to Polydactyly; Bardet Biedl syndrome 5, 615983 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.81 | BBS5 | Eleanor Williams Mode of inheritance for gene: BBS5 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | CCDC40 | Matthew Edwards reviewed gene: CCDC40: Rating: GREEN; Mode of pathogenicity: None; Publications: 23255504, 21131974; Phenotypes: OMIM 613808 Ciliary dyskinesia, primary, 15; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.469 | BSCL2 | Rebecca Foulger Added comment: Comment on mode of inheritance: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that MOI should change from 'BOTH monoallelic and biallelic' to 'BIALLELIC': just one monoallelic case so far, which could be a false positive. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.469 | BSCL2 | Rebecca Foulger Mode of inheritance for gene: BSCL2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.468 | NDUFA1 | Rebecca Foulger Added comment: Comment on mode of inheritance: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that MOI should be updated from XLR to XLD. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.468 | NDUFA1 | Rebecca Foulger Mode of inheritance for gene: NDUFA1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.467 | NSDHL | Rebecca Foulger Added comment: Comment on mode of inheritance: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that MOI should remain as XLR. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.467 | NSDHL | Rebecca Foulger Mode of inheritance for gene: NSDHL was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.466 | ADAR | Rebecca Foulger Added comment: Comment on mode of inheritance: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that MOI should remain as BIALLELIC: No current evidence for seizures in monoallelic cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.466 | ADAR | Rebecca Foulger Mode of inheritance for gene: ADAR was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.465 | DNAJC5 | Rebecca Foulger Classified gene: DNAJC5 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.465 | DNAJC5 | Rebecca Foulger Gene: dnajc5 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.464 | DNAJC5 | Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Demoted from Green to Amber.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Seizures present later. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.464 | DNAJC5 | Rebecca Foulger commented on gene: DNAJC5: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.464 | SGSH | Rebecca Foulger commented on gene: SGSH: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Kept rating as Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.464 | EXT2 | Rebecca Foulger Classified gene: EXT2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.464 | EXT2 | Rebecca Foulger Gene: ext2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.463 | EXT2 | Rebecca Foulger commented on gene: EXT2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Seizures not a presenting feature. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.463 | CLPB | Rebecca Foulger Classified gene: CLPB as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.463 | CLPB | Rebecca Foulger Gene: clpb has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.462 | CLPB | Rebecca Foulger commented on gene: CLPB: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Although there are three cases, most patients don't have seizures. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.462 | TMEM70 | Rebecca Foulger Classified gene: TMEM70 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.462 | TMEM70 | Rebecca Foulger Gene: tmem70 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.461 | TMEM70 | Rebecca Foulger commented on gene: TMEM70: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Insufficient seizure evidence. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.461 | SLC6A19 | Rebecca Foulger Classified gene: SLC6A19 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.461 | SLC6A19 | Rebecca Foulger Gene: slc6a19 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.460 | SLC6A19 | Rebecca Foulger commented on gene: SLC6A19: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Epilepsy is not a key feature. Demoted from Green to Red. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.460 | SLC35A1 | Rebecca Foulger Publications for gene: SLC35A1 were set to 23873973; 15576474; 28856833; 30115659 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.459 | SLC35A1 | Rebecca Foulger Classified gene: SLC35A1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.459 | SLC35A1 | Rebecca Foulger Gene: slc35a1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.458 | SLC35A1 | Rebecca Foulger commented on gene: SLC35A1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.458 | SCO2 | Rebecca Foulger Publications for gene: SCO2 were set to 10545952; 10749987; 18924171 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.457 | SCO2 | Rebecca Foulger Classified gene: SCO2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.457 | SCO2 | Rebecca Foulger Gene: sco2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.456 | SCO2 | Rebecca Foulger commented on gene: SCO2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.456 | SCO1 | Rebecca Foulger Classified gene: SCO1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.456 | SCO1 | Rebecca Foulger Gene: sco1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.455 | SCO1 | Rebecca Foulger commented on gene: SCO1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.455 | QDPR | Rebecca Foulger Classified gene: QDPR as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.455 | QDPR | Rebecca Foulger Gene: qdpr has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.454 | QDPR | Rebecca Foulger commented on gene: QDPR: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.454 | PRODH | Rebecca Foulger Classified gene: PRODH as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.454 | PRODH | Rebecca Foulger Gene: prodh has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.453 | PRODH | Rebecca Foulger commented on gene: PRODH: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.453 | PEX7 | Rebecca Foulger Classified gene: PEX7 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.453 | PEX7 | Rebecca Foulger Gene: pex7 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.452 | PEX7 | Rebecca Foulger commented on gene: PEX7: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.452 | PEX12 | Rebecca Foulger Classified gene: PEX12 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.452 | PEX12 | Rebecca Foulger Gene: pex12 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.451 | PEX12 | Rebecca Foulger commented on gene: PEX12: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted all PEX genes from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.451 | PEX10 | Rebecca Foulger Publications for gene: PEX10 were set to 20695019 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.450 | PEX10 | Rebecca Foulger Classified gene: PEX10 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.450 | PEX10 | Rebecca Foulger Gene: pex10 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.449 | PEX10 | Rebecca Foulger commented on gene: PEX10: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted all PEX genes from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.449 | PEX1 | Rebecca Foulger Classified gene: PEX1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.449 | PEX1 | Rebecca Foulger Gene: pex1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.448 | PEX1 | Rebecca Foulger commented on gene: PEX1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted all PEX genes from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.448 | MTR | Rebecca Foulger Classified gene: MTR as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.448 | MTR | Rebecca Foulger Gene: mtr has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.447 | MTR | Rebecca Foulger commented on gene: MTR: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Metabolic phenotype with failure to thrive, with seizures presenting later. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.447 | IDH2 | Rebecca Foulger Classified gene: IDH2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.447 | IDH2 | Rebecca Foulger Gene: idh2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.446 | IDH2 | Rebecca Foulger commented on gene: IDH2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green.Refers to glioma patients: not a seizure disorder. Demoted from Green to RED. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.446 | HLCS | Rebecca Foulger Classified gene: HLCS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.446 | HLCS | Rebecca Foulger Gene: hlcs has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.445 | HLCS | Rebecca Foulger commented on gene: HLCS: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.445 | GSS | Rebecca Foulger Classified gene: GSS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.445 | GSS | Rebecca Foulger Gene: gss has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.444 | GSS | Rebecca Foulger commented on gene: GSS: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.444 | GLYCTK | Rebecca Foulger Classified gene: GLYCTK as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.444 | GLYCTK | Rebecca Foulger Gene: glyctk has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.443 | GLYCTK | Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Bordeline cases from literature, variable phenotype and needs better genotype:phenotype correlation. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.443 | GLYCTK | Rebecca Foulger commented on gene: GLYCTK: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.443 | GFM1 | Rebecca Foulger Classified gene: GFM1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.443 | GFM1 | Rebecca Foulger Gene: gfm1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.442 | GFM1 | Rebecca Foulger commented on gene: GFM1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.442 | GCH1 | Rebecca Foulger Classified gene: GCH1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.442 | GCH1 | Rebecca Foulger Gene: gch1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.441 | GCH1 | Rebecca Foulger commented on gene: GCH1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.441 | FH | Rebecca Foulger Classified gene: FH as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.441 | FH | Rebecca Foulger Gene: fh has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.440 | FH | Rebecca Foulger commented on gene: FH: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.440 | FAR1 | Rebecca Foulger Classified gene: FAR1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.440 | FAR1 | Rebecca Foulger Gene: far1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.439 | FAR1 | Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Borderline evidence and variable phenotype. Requires better genotype:phenotype correlation. Demoted from Green to Amber.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.439 | FAR1 | Rebecca Foulger commented on gene: FAR1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Borderline evidence and variable phenotype. Requires better genotype:phenotype correlation. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.439 | DOLK | Rebecca Foulger Classified gene: DOLK as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.439 | DOLK | Rebecca Foulger Gene: dolk has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.438 | DOLK | Rebecca Foulger commented on gene: DOLK: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.438 | CYP27A1 | Rebecca Foulger Classified gene: CYP27A1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.438 | CYP27A1 | Rebecca Foulger Gene: cyp27a1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.437 | CYP27A1 | Rebecca Foulger commented on gene: CYP27A1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. prominent phenotype is dystonia/ataxia. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.437 | PTS | Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Seizures may present before 9 months, and could be the primary presentation in these cases. Promoted from Amber to Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Seizures may present before 9 months, and could be the primary presentation in these cases. Since the last group review, PTS has also been promoted to Green on the 'Inborn errors of metabolism' panel (v 1.407). Promoted PTS from Amber to Green on the epilepsy panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.437 | PTS | Rebecca Foulger Classified gene: PTS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.437 | PTS | Rebecca Foulger Gene: pts has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.436 | PTS | Rebecca Foulger commented on gene: PTS: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Seizures may present before 9 months, and could be the primary presentation in these cases. Promoted from Amber to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.436 | RRM2B | Rebecca Foulger commented on gene: RRM2B: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Kept rating as Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.436 | PEX5 | Rebecca Foulger commented on gene: PEX5: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Kept rating as Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.436 | GTPBP3 | Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Kept rating as Amber.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Kept rating as Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.436 | GTPBP3 | Rebecca Foulger commented on gene: GTPBP3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Kept rating as Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.436 | DPM2 | Rebecca Foulger commented on gene: DPM2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Kept rating as Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.436 | SCN9A | Rebecca Foulger Classified gene: SCN9A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.436 | SCN9A | Rebecca Foulger Gene: scn9a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.435 | SCN9A | Rebecca Foulger commented on gene: SCN9A: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Demoted SCN9A from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.435 | KCNA1 | Rebecca Foulger Classified gene: KCNA1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.435 | KCNA1 | Rebecca Foulger Gene: kcna1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.434 | KCNA1 | Rebecca Foulger commented on gene: KCNA1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Demoted KCNA1 from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.434 | FLNA | Rebecca Foulger Added comment: Comment on mode of inheritance: At the Webex call 22nd November 2019, it was notes that want to target FEMALES ONLY for the Heterotopia periventricular phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.434 | FLNA | Rebecca Foulger Mode of inheritance for gene: FLNA was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.433 | FLNA | Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Kept rating of FLNA as Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy, and following Green ratings by Alisdair McNeill and Alison Callaway: Agreed that there is enough evidence to rate this gene Green. Kept rating of FLNA as Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.433 | FLNA | Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Kept rating as Green.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Kept rating of FLNA as Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.433 | FLNA | Rebecca Foulger commented on gene: FLNA: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Kept rating as Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.433 | CACNA2D2 | Rebecca Foulger Phenotypes for gene: CACNA2D2 were changed from Absence epilepsy to Absence epilepsy; Cerebellar atrophy with seizures and variable developmental delay, 618501 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.432 | CACNA2D2 | Rebecca Foulger Classified gene: CACNA2D2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.432 | CACNA2D2 | Rebecca Foulger Gene: cacna2d2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.431 | CACNA2D2 | Rebecca Foulger commented on gene: CACNA2D2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Promoted from Amber to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.431 | ALG8 | Rebecca Foulger commented on gene: ALG8: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Although there is inconsistency amongst patients, there are sufficient cases for a Green rating. Kept rating as Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.431 | TDP2 | Rebecca Foulger commented on gene: TDP2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.431 | GOT2 | Rebecca Foulger Classified gene: GOT2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.431 | GOT2 | Rebecca Foulger Gene: got2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.430 | GOT2 | Rebecca Foulger commented on gene: GOT2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Promoted from Amber to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.430 | HNRNPR | Rebecca Foulger Mode of inheritance for gene: HNRNPR was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.429 | HNRNPR | Rebecca Foulger Classified gene: HNRNPR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.429 | HNRNPR | Rebecca Foulger Gene: hnrnpr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.428 | HNRNPR | Rebecca Foulger commented on gene: HNRNPR: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Although obvious dysmoprhism is associated with the phenotype, it meets the criteria for a Green rating. Promoted from Amber to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.428 | ZNF142 | Rebecca Foulger Classified gene: ZNF142 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.428 | ZNF142 | Rebecca Foulger Gene: znf142 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.427 | ZNF142 | Rebecca Foulger commented on gene: ZNF142: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Sufficient cases for inclusion. Promoted from Amber to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.427 | TRRAP | Rebecca Foulger commented on gene: TRRAP: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Seizures aren't a prominent feature. Kept rating as Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.427 | NPRL2 | Rebecca Foulger Classified gene: NPRL2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.427 | NPRL2 | Rebecca Foulger Gene: nprl2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.426 | NPRL2 | Rebecca Foulger commented on gene: NPRL2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Sufficient cases to support gene:disease association, although unaffected carriers/incomplete penetrance may make variant interpretation difficult. Promoted from Amber to Green with the option to review on subsequent versions. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.426 | HCN2 | Rebecca Foulger Marked gene: HCN2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.426 | HCN2 | Rebecca Foulger Gene: hcn2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.426 | HCN2 | Rebecca Foulger commented on gene: HCN2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green. Although this is a borderline case with questions over phenotype segregation, there are sufficient cases to support inclusion. Although seizures aren’t one of the cardinal phenotypes, most cases will be trios and therefore there will be less issues in being inclusive. Kept rating of HCN2 as Green with the option of review on subsequent panel versions. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.426 | AFF3 | Rebecca Foulger Classified gene: AFF3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.426 | AFF3 | Rebecca Foulger Gene: aff3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.425 | AFF3 | Rebecca Foulger commented on gene: AFF3: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is enough evidence to rate this gene Green: Sufficient evidence in pre-print Voisin et al., 2019 article. Promoted AFF3 from Amber to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.80 | BBS4 | Eleanor Williams Classified gene: BBS4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.80 | BBS4 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.80 | BBS4 | Eleanor Williams Gene: bbs4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.79 | BBS4 | Eleanor Williams Phenotypes for gene: BBS4 were changed from Polydactyly to Polydactyly; Bardet-Biedl syndrome 4, 615982 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.78 | BBS4 | Eleanor Williams Mode of inheritance for gene: BBS4 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.77 | BBS2 | Eleanor Williams Classified gene: BBS2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.77 | BBS2 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.77 | BBS2 | Eleanor Williams Gene: bbs2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.76 | BBS2 | Eleanor Williams Phenotypes for gene: BBS2 were changed from Polydactyly to Polydactyly; Bardet-Biedl syndrome 2, 615981 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.75 | BBS2 | Eleanor Williams Mode of inheritance for gene: BBS2 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.74 | BBS12 | Eleanor Williams Classified gene: BBS12 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.74 | BBS12 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.74 | BBS12 | Eleanor Williams Gene: bbs12 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.73 | BBS12 | Eleanor Williams Phenotypes for gene: BBS12 were changed from Polydactyly to Polydactyly; Bardet Biedl syndrome 12, 615989 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.72 | BBS12 | Eleanor Williams Mode of inheritance for gene: BBS12 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.71 | BBS10 | Eleanor Williams Classified gene: BBS10 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.71 | BBS10 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.71 | BBS10 | Eleanor Williams Gene: bbs10 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.70 | BBS10 | Eleanor Williams Phenotypes for gene: BBS10 were changed from Polydactyly to Polydactyly; Bardet Biedl syndrome 10, 615987 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.69 | BBS10 | Eleanor Williams Mode of inheritance for gene: BBS10 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.68 | BBS1 | Eleanor Williams Classified gene: BBS1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.68 | BBS1 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.68 | BBS1 | Eleanor Williams Gene: bbs1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.67 | BBS1 | Eleanor Williams Phenotypes for gene: BBS1 were changed from Polydactyly; Bardet-Biedl syndrome 1209900 to Polydactyly; Bardet-Biedl syndrome 1 209900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.66 | ARL6 | Eleanor Williams Classified gene: ARL6 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.66 | ARL6 | Eleanor Williams Added comment: Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.66 | ARL6 | Eleanor Williams Gene: arl6 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Distal myopathies v1.12 | Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric motor neuronopathies v1.24 | Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rhabdomyolysis and metabolic muscle disorders v1.29 | Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital muscular dystrophy v1.69 | Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease; Component Of Super Panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myaesthenic syndrome v1.71 | Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease; Component Of Super Panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v1.100 | Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease; Component Of Super Panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital myopathy v1.192 | Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease; Component Of Super Panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other rare neuromuscular disorders v1.13 |
Ellen McDonagh Changed child panels to: Congenital myopathy; Limb girdle muscular dystrophy; Congenital myaesthenic syndrome; Congenital muscular dystrophy; Rhabdomyolysis and metabolic muscle disorders; Paediatric motor neuronopathies; Distal myopathies Panel types changed to GMS Rare Disease Virtual; Super Panel |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypotonic infant v3.1059 | Ellen McDonagh Changed child panels to: Intellectual disability; Inborn errors of metabolism; Congenital myopathy; Limb girdle muscular dystrophy; Congenital myaesthenic syndrome; Congenital muscular dystrophy; Rhabdomyolysis and metabolic muscle disorders; Paediatric motor neuronopathies; Distal myopathies | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy v1.338 | Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arthrogryposis v2.47 | Ellen McDonagh Panel types changed to Rare Disease 100K; Component Of Super Panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1107 | VAMP7 | Eleanor Williams Added comment: Comment on mode of inheritance: This gene is in the pseudoautosomal region shared between chromosomes X and Y. The mode of inheritance should therefore be set to Biallelic or Monoallelic once more cases establish the inheritance pattern. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1107 | VAMP7 | Eleanor Williams Mode of inheritance for gene: VAMP7 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1106 | SPRY3 | Eleanor Williams Added comment: Comment on mode of inheritance: This gene is in the pseudoautosomal region shared between chromosomes X and Y. The mode of inheritance should therefore be set to Biallelic or Monoallelic once more cases establish the inheritance pattern. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1106 | SPRY3 | Eleanor Williams Mode of inheritance for gene: SPRY3 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1105 | SLC25A6 | Eleanor Williams Added comment: Comment on mode of inheritance: This gene is in the pseudoautosomal region shared between chromosomes X and Y. The mode of inheritance should therefore be set to Biallelic or Monoallelic once more cases establish the inheritance pattern. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1105 | SLC25A6 | Eleanor Williams Mode of inheritance for gene: SLC25A6 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1104 | P2RY8 | Eleanor Williams Added comment: Comment on mode of inheritance: This gene is in the pseudoautosomal region shared between chromosomes X and Y. The mode of inheritance should therefore be set to Biallelic or Monoallelic once more cases establish the inheritance pattern. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1104 | P2RY8 | Eleanor Williams Mode of inheritance for gene: P2RY8 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1103 | PLCXD1 | Eleanor Williams Added comment: Comment on mode of inheritance: This gene is in the pseudoautosomal region shared between chromosomes X and Y. The mode of inheritance should therefore be set to Biallelic or Monoallelic once more cases establish the inheritance pattern. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1103 | PLCXD1 | Eleanor Williams Mode of inheritance for gene: PLCXD1 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.109 | Louise Daugherty removed STR:ATXN1_ATTCT from the panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset neurodegenerative disorder v1.108 | Louise Daugherty removed STR:ATXN10_CAG from the panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1102 | DMXL2 |
Konstantinos Varvagiannis changed review comment from: This gene can be considered for upgrade to green rating (ID and epilepsy with >=4 relevant individuals/families/variants and >=2 studies, role of the protein, effect of variants in most cases demonstrated, phenotypic similarities with other disorders affecting autophagy, some evidence from animal models, etc). Rare heterozygous variants disrupting DMXL2 (intragenic losses/gains, SNVs, CNVs affecting also additional genes) have been reported in individuals with variable neurodevelopmental disorders (ASD and ID) or psychiatric phenotypes [Costain et al. 2019 - PMID: 30732576 - summarized in Table 1]. (Highly) variable expressivity and possibly incomplete penetrance were proposed in the respective study. As a result evidence for ID/seizures due to monoallelic variants appears to be relatively limited. DD, ID and (probably) epilepsy appear however to be features in several individuals with biallelic pathogenic variants as summarized in the studies below. OMIM recently added a relevant entry with the DMXL2-associated phenotypes being the following: - Epileptic encephalopathy, early infantile, 81; EIEE81 - 618663 (AD) [based on refs 2,3] - ?Deafness, autosomal dominant 71 - 617605 (AD) [DD/ID/seizures are not part of the phenotype] - ?Polyendocrine-polyneuropathy syndrome - 616113 (AR) [based on ref1] DMXL2 is not associated with any phenotype in G2P. In SysID it is listed as a candidate ID gene based on the report by Tata et al (ref1). This gene is included in some gene panels for ID. [1] Tata el al. (2014 - PMID: 25248098) reported on 3 sibs born to consanguineous Senegalese parents, presenting with a progressive endocrine and neurodevelopmental disorder. Features incl. incomplete puberty, central hypothyroidism, abnormal glucose regulation, moderate ID (3/3) and peripheral polyneuropathy. Seizures were not part of the phenotype. Linkage analysis suggested 2 candidate regions on chromosomes 13 and 15 with a LOD score of 2.5. High throughput sequencing of genes within these regions (~500) in an affected member and parent revealed a 15 bp in-frame deletion of DMXL2 (NM_015263.4:c.5827_5841del / p.Asp1943_Ser1947del). Sanger sequencing of other affected and unaffected members supported AR inheritance. RT-qPCR demonstrated that DMXL2 mRNA levels in blood lymphocytes were significantly lower in homozygous patients compared to heterozygous or wt family members or controls. The authors demonstrated that the encoded protein (rabconnectin-3a) is a synaptic protein (expressed in exocytosis vesicles) at the ends of axons of GnRH producing neurons. Neuron-specific deletion of one allele in mice resulted in delayed puberty and very low fertility. Adult mice had lower number of GnRH neurons in hypothalamus. siRNA-mediated downregulation of Dmxl2 expression in an insulin-secreting cell line resulted in only slight insulin secretion in response to augmenting concentrations of glucose, providing evidence of involvement of the protein in control of regulated insulin secretion. ----------- [2] Maddirevula et al. (2019 - PMID: 30237576) reported briefly on a 36 months old boy, born to consanguineous parents, homozygous for a frameshift DMXL2 variant [individual 17-3220 | NM_001174117.1:c.4349_4350insTTACATGA or p.(Glu1450Aspfs*23)]. Features included focal seizures (onset at the age of 3m) with subsequent global DD, absent eye contact, cerebral atrophy and macrocephaly. This individual was identified following re-evaluation of exome data in a database of ~1550 exomes specifically for homozygous variants that would have been classified earlier as LP/P if the respective gene had sufficient evidence for association with a disorder. The family was not reported to have other affected members. As the authors noted, the boy was not known to have the multi-endocrine abnormalities reported by Tata et al. There are no additional information provided (eg. on confirmation of variants, etc). ----------- [3] Esposito et al. (2019 - PMID: 31688942) report on 3 sibling pairs (all 3 families unrelated) with biallelic DMXL2 mutations and summarize previous evidence on the gene and the DMXL2-related phenotypes. All presented a highly similar phenotype of Ohtahara syndrome (seizures with onset in the first days of life, tonic/myoclonic/occasionaly focal, burst-suppression upon EEG), profound DD/ID, quadriparesis, sensorineural hearing loss and presence of dysmorphic features. Sibs from 2 families presented evidence of peripheral polyneuropathy. Early brain MRIs revealed thin CC and hypomyelination in all, with later scans suggestive of gray and white matter shrinkage with leukoencephalopathy. None achieved developmental skills following birth with 5/6 deceased by the age of 9 years. Exome sequencing revealed biallelic DMXL2 variants in all, with compatible parental segregation studies (NM_015263.3): - Fam1 (2 sibs) : c.5135C>T (p.Ala1712Val) in trans with c.4478C>G (p.Ser1493*) - Fam2 (2 sibs) : homozygosity for c.4478C>A (p.Ser1493*) - Fam3 (2 sibs) : homozygosity for c.7518-1G>A Heterozygous parents (aged 39-59) did not exhibit hearing impairment [report of a single multigenerational family by Chen et al (2017 - PMID: 27657680) where a heterozygous missense variant segregated with hearing loss - respective OMIM entry: ?Deafness, autosomal dominant 71 - 617605]. In patients' fibroblasts, effect of the variants on mRNA/protein expression was demonstrated with mRNA expressed only in a patient from family 1, and degraded/absent for the 2 stopgain SNVs affecting codon 1493. Skipping of ex31 leading to frameshift/introduction of a PTC was shown for the splice variant (p.Trp2508Argfs*4 secondary to c.7518-1G>A). Protein was also absent upon western-blot. DMXL2 encodes a vesicular protein, DmX-Like protein 2 or rabconnectin-3a (cited Tata et al). The gene is expressed in brain ( https://www.gtexportal.org/home/gene/DMXL2 ). As Esposito et al comment, it is known to regulate the trafficking and activity of v-ATPase the latter having a role in acidifying intracellular organelles and promoting endosomal maturation (cited PMIDs : 25248098, 19758563, 22875945, 24802872). In line with this, staining of patients' fibroblasts using the acidotropic dye LysoTracker demonstrated increased signal, reversed by re-expression of DMXL2 protein. Overall an acidic shift in pH with impairment of lysosomal structures and function was suggested. The authors provided additional evidence for altered lysosomal function and associated autophagy with accumulation of autophagy receptors (eg p62) and substrates (polyubiquitinated proteins). Vacuolization and accumulation of atypical fusion-like structures was shown upon ultrastractural analysis. shRNA-mediated downregulation/silencing of Dmxl2 in mouse hippocampal neurons resulted also in altered lysosomal structures and defective autophagy. The neurons exhibited impaired neurite elongation and synapse formation. The authors suggest similarities with Vici syndrome, where biallelic EPG5 mutations result in autophagic defects and clinical manifestations of DD/ID/epilepsy. Dmxl2 homozygous ko mice display embryonic lethality with heterozygous mice displaying macrocephaly and corpus callosum dysplasia (cited PMIDs: 25248098, 30735494) .; to: This gene can be considered for upgrade to green rating (ID and epilepsy with >=4 relevant individuals/families/variants and >=2 studies, role of the protein, effect of variants in most cases demonstrated, phenotypic similarities with other disorders affecting autophagy, some evidence from animal models, etc). Rare heterozygous variants disrupting DMXL2 (intragenic losses/gains, SNVs, CNVs affecting also additional genes) have been reported in individuals with variable neurodevelopmental disorders (ASD and ID) or psychiatric phenotypes [Costain et al. 2019 - PMID: 30732576 - summarized in Table 1]. (Highly) variable expressivity and possibly incomplete penetrance were proposed in the respective study. As a result evidence for ID/seizures due to monoallelic variants appears to be relatively limited. DD, ID and (probably) epilepsy appear however to be features in several individuals with biallelic pathogenic variants as summarized in the studies below. OMIM recently added a relevant entry with the DMXL2-associated phenotypes being the following: - Epileptic encephalopathy, early infantile, 81; EIEE81 - 618663 (AR) [based on refs 2,3] - ?Deafness, autosomal dominant 71 - 617605 (AD) [DD/ID/seizures are not part of the phenotype] - ?Polyendocrine-polyneuropathy syndrome - 616113 (AR) [based on ref1] DMXL2 is not associated with any phenotype in G2P. In SysID it is listed as a candidate ID gene based on the report by Tata et al (ref1). This gene is included in some gene panels for ID. [1] Tata el al. (2014 - PMID: 25248098) reported on 3 sibs born to consanguineous Senegalese parents, presenting with a progressive endocrine and neurodevelopmental disorder. Features incl. incomplete puberty, central hypothyroidism, abnormal glucose regulation, moderate ID (3/3) and peripheral polyneuropathy. Seizures were not part of the phenotype. Linkage analysis suggested 2 candidate regions on chromosomes 13 and 15 with a LOD score of 2.5. High throughput sequencing of genes within these regions (~500) in an affected member and parent revealed a 15 bp in-frame deletion of DMXL2 (NM_015263.4:c.5827_5841del / p.Asp1943_Ser1947del). Sanger sequencing of other affected and unaffected members supported AR inheritance. RT-qPCR demonstrated that DMXL2 mRNA levels in blood lymphocytes were significantly lower in homozygous patients compared to heterozygous or wt family members or controls. The authors demonstrated that the encoded protein (rabconnectin-3a) is a synaptic protein (expressed in exocytosis vesicles) at the ends of axons of GnRH producing neurons. Neuron-specific deletion of one allele in mice resulted in delayed puberty and very low fertility. Adult mice had lower number of GnRH neurons in hypothalamus. siRNA-mediated downregulation of Dmxl2 expression in an insulin-secreting cell line resulted in only slight insulin secretion in response to augmenting concentrations of glucose, providing evidence of involvement of the protein in control of regulated insulin secretion. ----------- [2] Maddirevula et al. (2019 - PMID: 30237576) reported briefly on a 36 months old boy, born to consanguineous parents, homozygous for a frameshift DMXL2 variant [individual 17-3220 | NM_001174117.1:c.4349_4350insTTACATGA or p.(Glu1450Aspfs*23)]. Features included focal seizures (onset at the age of 3m) with subsequent global DD, absent eye contact, cerebral atrophy and macrocephaly. This individual was identified following re-evaluation of exome data in a database of ~1550 exomes specifically for homozygous variants that would have been classified earlier as LP/P if the respective gene had sufficient evidence for association with a disorder. The family was not reported to have other affected members. As the authors noted, the boy was not known to have the multi-endocrine abnormalities reported by Tata et al. There are no additional information provided (eg. on confirmation of variants, etc). ----------- [3] Esposito et al. (2019 - PMID: 31688942) report on 3 sibling pairs (all 3 families unrelated) with biallelic DMXL2 mutations and summarize previous evidence on the gene and the DMXL2-related phenotypes. All presented a highly similar phenotype of Ohtahara syndrome (seizures with onset in the first days of life, tonic/myoclonic/occasionaly focal, burst-suppression upon EEG), profound DD/ID, quadriparesis, sensorineural hearing loss and presence of dysmorphic features. Sibs from 2 families presented evidence of peripheral polyneuropathy. Early brain MRIs revealed thin CC and hypomyelination in all, with later scans suggestive of gray and white matter shrinkage with leukoencephalopathy. None achieved developmental skills following birth with 5/6 deceased by the age of 9 years. Exome sequencing revealed biallelic DMXL2 variants in all, with compatible parental segregation studies (NM_015263.3): - Fam1 (2 sibs) : c.5135C>T (p.Ala1712Val) in trans with c.4478C>G (p.Ser1493*) - Fam2 (2 sibs) : homozygosity for c.4478C>A (p.Ser1493*) - Fam3 (2 sibs) : homozygosity for c.7518-1G>A Heterozygous parents (aged 39-59) did not exhibit hearing impairment [report of a single multigenerational family by Chen et al (2017 - PMID: 27657680) where a heterozygous missense variant segregated with hearing loss - respective OMIM entry: ?Deafness, autosomal dominant 71 - 617605]. In patients' fibroblasts, effect of the variants on mRNA/protein expression was demonstrated with mRNA expressed only in a patient from family 1, and degraded/absent for the 2 stopgain SNVs affecting codon 1493. Skipping of ex31 leading to frameshift/introduction of a PTC was shown for the splice variant (p.Trp2508Argfs*4 secondary to c.7518-1G>A). Protein was also absent upon western-blot. DMXL2 encodes a vesicular protein, DmX-Like protein 2 or rabconnectin-3a (cited Tata et al). The gene is expressed in brain ( https://www.gtexportal.org/home/gene/DMXL2 ). As Esposito et al comment, it is known to regulate the trafficking and activity of v-ATPase the latter having a role in acidifying intracellular organelles and promoting endosomal maturation (cited PMIDs : 25248098, 19758563, 22875945, 24802872). In line with this, staining of patients' fibroblasts using the acidotropic dye LysoTracker demonstrated increased signal, reversed by re-expression of DMXL2 protein. Overall an acidic shift in pH with impairment of lysosomal structures and function was suggested. The authors provided additional evidence for altered lysosomal function and associated autophagy with accumulation of autophagy receptors (eg p62) and substrates (polyubiquitinated proteins). Vacuolization and accumulation of atypical fusion-like structures was shown upon ultrastractural analysis. shRNA-mediated downregulation/silencing of Dmxl2 in mouse hippocampal neurons resulted also in altered lysosomal structures and defective autophagy. The neurons exhibited impaired neurite elongation and synapse formation. The authors suggest similarities with Vici syndrome, where biallelic EPG5 mutations result in autophagic defects and clinical manifestations of DD/ID/epilepsy. Dmxl2 homozygous ko mice display embryonic lethality with heterozygous mice displaying macrocephaly and corpus callosum dysplasia (cited PMIDs: 25248098, 30735494) . |
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| Early onset or syndromic epilepsy v1.425 | SCN9A | Alison Callaway reviewed gene: SCN9A: Rating: AMBER; Mode of pathogenicity: None; Publications: 30834459, 29500686; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.425 | ALG8 | Rebecca Foulger changed review comment from: 26066342 (Hock et al., 2015) describe 3 new patients with ALG8-CDG, provide an update on 2 previous patients and summarise 10 previous patients. The 15 patients total included 4 pairs of siblings. Brain involvement (psychomotor disability or seizures or ataxia or structural anomalies) were seen in 12/13 patients.; to: 26066342 (Hock et al., 2015) describe 3 new patients with ALG8-CDG, provide an update on 2 previous patients and summarise 10 previous patients. The 15 patients total included 4 pairs of siblings. Brain involvement (psychomotor disability or seizures or ataxia or structural anomalies) was seen in 12/13 patients. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.425 | DMXL2 |
Konstantinos Varvagiannis changed review comment from: This gene can be considered for inclusion in both ID and epilepsy panels probably with green (ID and epilepsy with >=4 relevant individuals/families/variants and >=2 studies, role of the protein, effect of variants in most cases demonstrated, phenotypic similarities with other disorders affecting autophagy, some evidence from animal models, etc) or amber rating. Rare heterozygous variants disrupting DMXL2 (intragenic losses/gains, SNVs, CNVs affecting also additional genes) have been reported in individuals with variable neurodevelopmental disorders (ASD and ID) or psychiatric phenotypes [Costain et al. 2019 - PMID: 30732576 - summarized in Table 1]. (Highly) variable expressivity and possibly incomplete penetrance were proposed in the respective study. As a result evidence for ID/seizures due to monoallelic variants appears to be relatively limited. DD, ID and (probably) epilepsy appear however to be constant features in several individuals with biallelic pathogenic variants as summarized in the studies below. OMIM recently added a relevant entry with the DMXL2-associated phenotypes being the following: - Epileptic encephalopathy, early infantile, 81; EIEE81 - 618663 (AD) [based on refs 2,3] - ?Deafness, autosomal dominant 71 - 617605 (AD) [DD/ID/seizures are not part of the phenotype] - ?Polyendocrine-polyneuropathy syndrome - 616113 (AR) [based on ref1] DMXL2 is not associated with any phenotype in G2P. In SysID it is listed as a candidate ID gene based on the report by Tata et al (ref1). This gene is included in some gene panels for ID. [1] Tata el al. (2014 - PMID: 25248098) reported on 3 sibs born to consanguineous Senegalese parents, presenting with a progressive endocrine and neurodevelopmental disorder. Features incl. incomplete puberty, central hypothyroidism, abnormal glucose regulation, moderate ID (3/3) and peripheral polyneuropathy. Seizures were not part of the phenotype. Linkage analysis suggested 2 candidate regions on chromosomes 13 and 15 with a LOD score of 2.5. High throughput sequencing of genes within these regions (~500) in an affected member and parent revealed a 15 bp in-frame deletion of DMXL2 (NM_015263.4:c.5827_5841del / p.Asp1943_Ser1947del). Sanger sequencing of other affected and unaffected members supported AR inheritance. RT-qPCR demonstrated that DMXL2 mRNA levels in blood lymphocytes were significantly lower in homozygous patients compared to heterozygous or wt family members or controls. The authors demonstrated that the encoded protein (rabconnectin-3a) is a synaptic protein (expressed in exocytosis vesicles) at the ends of axons of GnRH producing neurons. Neuron-specific deletion of one allele in mice resulted in delayed puberty and very low fertility. Adult mice had lower number of GnRH neurons in hypothalamus. siRNA-mediated downregulation of Dmxl2 expression in an insulin-secreting cell line resulted in only slight insulin secretion in response to augmenting concentrations of glucose, providing evidence of involvement of the protein in control of regulated insulin secretion. ----------- [2] Maddirevula et al. (2019 - PMID: 30237576) reported briefly on a 36 months old boy, born to consanguineous parents, homozygous for a frameshift DMXL2 variant [individual 17-3220 | NM_001174117.1:c.4349_4350insTTACATGA or p.(Glu1450Aspfs*23)]. Features included focal seizures (onset at the age of 3m) with subsequent global DD, absent eye contact, cerebral atrophy and macrocephaly. This individual was identified following re-evaluation of exome data in a database of ~1550 exomes specifically for homozygous variants that would have been classified earlier as LP/P if the respective gene had sufficient evidence for association with a disorder. The family was not reported to have other affected members. As the authors noted, the boy was not known to have the multi-endocrine abnormalities reported by Tata et al. There are no additional information provided (eg. on confirmation of variants, etc). ----------- [3] Esposito et al. (2019 - PMID: 31688942) report on 3 sibling pairs (all 3 families unrelated) with biallelic DMXL2 mutations and summarize previous evidence on the gene and the DMXL2-related phenotypes. All presented a highly similar phenotype of Ohtahara syndrome (seizures with onset in the first days of life, tonic/myoclonic/occasionaly focal, burst-suppression upon EEG), profound DD/ID, quadriparesis, sensorineural hearing loss and presence of dysmorphic features. Sibs from 2 families presented evidence of peripheral polyneuropathy. Early brain MRIs revealed thin CC and hypomyelination in all, with later scans suggestive of gray and white matter shrinkage with leukoencephalopathy. None achieved developmental skills following birth with 5/6 deceased by the age of 9 years. Exome sequencing revealed biallelic DMXL2 variants in all, with compatible parental segregation studies (NM_015263.3): - Fam1 (2 sibs) : c.5135C>T (p.Ala1712Val) in trans with c.4478C>G (p.Ser1493*) - Fam2 (2 sibs) : homozygosity for c.4478C>A (p.Ser1493*) - Fam3 (2 sibs) : homozygosity for c.7518-1G>A Heterozygous parents (aged 39-59) did not exhibit hearing impairment [report of a single multigenerational family by Chen et al (2017 - PMID: 27657680) where a heterozygous missense variant segregated with hearing loss - respective OMIM entry: ?Deafness, autosomal dominant 71 - 617605]. In patients' fibroblasts, effect of the variants on mRNA/protein expression was demonstrated with mRNA expressed only in a patient from family 1, and degraded/absent for the 2 stopgain SNVs affecting codon 1493. Skipping of ex31 leading to frameshift/introduction of a PTC was shown for the splice variant (p.Trp2508Argfs*4 secondary to c.7518-1G>A). Protein was also absent upon western-blot. DMXL2 encodes a vesicular protein, DmX-Like protein 2 or rabconnectin-3a (cited Tata et al). The gene is expressed in brain ( https://www.gtexportal.org/home/gene/DMXL2 ). As Esposito et al comment, it is known to regulate the trafficking and activity of v-ATPase the latter having a role in acidifying intracellular organelles and promoting endosomal maturation (cited PMIDs : 25248098, 19758563, 22875945, 24802872). In line with this, staining of patients' fibroblasts using the acidotropic dye LysoTracker demonstrated increased signal, reversed by re-expression of DMXL2 protein. Overall an acidic shift in pH with impairment of lysosomal structures and function was suggested. The authors provided additional evidence for altered lysosomal function and associated autophagy with accumulation of autophagy receptors (eg p62) and substrates (polyubiquitinated proteins). Vacuolization and accumulation of atypical fusion-like structures was shown upon ultrastractural analysis. shRNA-mediated downregulation/silencing of Dmxl2 in mouse hippocampal neurons resulted also in altered lysosomal structures and defective autophagy. The neurons exhibited impaired neurite elongation and synapse formation. The authors suggest similarities with Vici syndrome, where biallelic EPG5 mutations result in autophagic defects and clinical manifestations of DD/ID/epilepsy. Dmxl2 homozygous ko mice display embryonic lethality with heterozygous mice displaying macrocephaly and corpus callosum dysplasia (cited PMIDs: 25248098, 30735494) . Sources: Literature; to: This gene can be considered for inclusion in both ID and epilepsy panels probably with green (ID and epilepsy with >=4 relevant individuals/families/variants and >=2 studies, role of the protein, effect of variants in most cases demonstrated, phenotypic similarities with other disorders affecting autophagy, some evidence from animal models, etc) or amber rating. Rare heterozygous variants disrupting DMXL2 (intragenic losses/gains, SNVs, CNVs affecting also additional genes) have been reported in individuals with variable neurodevelopmental disorders (ASD and ID) or psychiatric phenotypes [Costain et al. 2019 - PMID: 30732576 - summarized in Table 1]. (Highly) variable expressivity and possibly incomplete penetrance were proposed in the respective study. As a result evidence for ID/seizures due to monoallelic variants appears to be relatively limited. DD, ID and (probably) epilepsy appear however to be constant features in several individuals with biallelic pathogenic variants as summarized in the studies below. OMIM recently added a relevant entry with the DMXL2-associated phenotypes being the following: - Epileptic encephalopathy, early infantile, 81; EIEE81 - 618663 (AR) [based on refs 2,3] - ?Deafness, autosomal dominant 71 - 617605 (AD) [DD/ID/seizures are not part of the phenotype] - ?Polyendocrine-polyneuropathy syndrome - 616113 (AR) [based on ref1] DMXL2 is not associated with any phenotype in G2P. In SysID it is listed as a candidate ID gene based on the report by Tata et al (ref1). This gene is included in some gene panels for ID. [1] Tata el al. (2014 - PMID: 25248098) reported on 3 sibs born to consanguineous Senegalese parents, presenting with a progressive endocrine and neurodevelopmental disorder. Features incl. incomplete puberty, central hypothyroidism, abnormal glucose regulation, moderate ID (3/3) and peripheral polyneuropathy. Seizures were not part of the phenotype. Linkage analysis suggested 2 candidate regions on chromosomes 13 and 15 with a LOD score of 2.5. High throughput sequencing of genes within these regions (~500) in an affected member and parent revealed a 15 bp in-frame deletion of DMXL2 (NM_015263.4:c.5827_5841del / p.Asp1943_Ser1947del). Sanger sequencing of other affected and unaffected members supported AR inheritance. RT-qPCR demonstrated that DMXL2 mRNA levels in blood lymphocytes were significantly lower in homozygous patients compared to heterozygous or wt family members or controls. The authors demonstrated that the encoded protein (rabconnectin-3a) is a synaptic protein (expressed in exocytosis vesicles) at the ends of axons of GnRH producing neurons. Neuron-specific deletion of one allele in mice resulted in delayed puberty and very low fertility. Adult mice had lower number of GnRH neurons in hypothalamus. siRNA-mediated downregulation of Dmxl2 expression in an insulin-secreting cell line resulted in only slight insulin secretion in response to augmenting concentrations of glucose, providing evidence of involvement of the protein in control of regulated insulin secretion. ----------- [2] Maddirevula et al. (2019 - PMID: 30237576) reported briefly on a 36 months old boy, born to consanguineous parents, homozygous for a frameshift DMXL2 variant [individual 17-3220 | NM_001174117.1:c.4349_4350insTTACATGA or p.(Glu1450Aspfs*23)]. Features included focal seizures (onset at the age of 3m) with subsequent global DD, absent eye contact, cerebral atrophy and macrocephaly. This individual was identified following re-evaluation of exome data in a database of ~1550 exomes specifically for homozygous variants that would have been classified earlier as LP/P if the respective gene had sufficient evidence for association with a disorder. The family was not reported to have other affected members. As the authors noted, the boy was not known to have the multi-endocrine abnormalities reported by Tata et al. There are no additional information provided (eg. on confirmation of variants, etc). ----------- [3] Esposito et al. (2019 - PMID: 31688942) report on 3 sibling pairs (all 3 families unrelated) with biallelic DMXL2 mutations and summarize previous evidence on the gene and the DMXL2-related phenotypes. All presented a highly similar phenotype of Ohtahara syndrome (seizures with onset in the first days of life, tonic/myoclonic/occasionaly focal, burst-suppression upon EEG), profound DD/ID, quadriparesis, sensorineural hearing loss and presence of dysmorphic features. Sibs from 2 families presented evidence of peripheral polyneuropathy. Early brain MRIs revealed thin CC and hypomyelination in all, with later scans suggestive of gray and white matter shrinkage with leukoencephalopathy. None achieved developmental skills following birth with 5/6 deceased by the age of 9 years. Exome sequencing revealed biallelic DMXL2 variants in all, with compatible parental segregation studies (NM_015263.3): - Fam1 (2 sibs) : c.5135C>T (p.Ala1712Val) in trans with c.4478C>G (p.Ser1493*) - Fam2 (2 sibs) : homozygosity for c.4478C>A (p.Ser1493*) - Fam3 (2 sibs) : homozygosity for c.7518-1G>A Heterozygous parents (aged 39-59) did not exhibit hearing impairment [report of a single multigenerational family by Chen et al (2017 - PMID: 27657680) where a heterozygous missense variant segregated with hearing loss - respective OMIM entry: ?Deafness, autosomal dominant 71 - 617605]. In patients' fibroblasts, effect of the variants on mRNA/protein expression was demonstrated with mRNA expressed only in a patient from family 1, and degraded/absent for the 2 stopgain SNVs affecting codon 1493. Skipping of ex31 leading to frameshift/introduction of a PTC was shown for the splice variant (p.Trp2508Argfs*4 secondary to c.7518-1G>A). Protein was also absent upon western-blot. DMXL2 encodes a vesicular protein, DmX-Like protein 2 or rabconnectin-3a (cited Tata et al). The gene is expressed in brain ( https://www.gtexportal.org/home/gene/DMXL2 ). As Esposito et al comment, it is known to regulate the trafficking and activity of v-ATPase the latter having a role in acidifying intracellular organelles and promoting endosomal maturation (cited PMIDs : 25248098, 19758563, 22875945, 24802872). In line with this, staining of patients' fibroblasts using the acidotropic dye LysoTracker demonstrated increased signal, reversed by re-expression of DMXL2 protein. Overall an acidic shift in pH with impairment of lysosomal structures and function was suggested. The authors provided additional evidence for altered lysosomal function and associated autophagy with accumulation of autophagy receptors (eg p62) and substrates (polyubiquitinated proteins). Vacuolization and accumulation of atypical fusion-like structures was shown upon ultrastractural analysis. shRNA-mediated downregulation/silencing of Dmxl2 in mouse hippocampal neurons resulted also in altered lysosomal structures and defective autophagy. The neurons exhibited impaired neurite elongation and synapse formation. The authors suggest similarities with Vici syndrome, where biallelic EPG5 mutations result in autophagic defects and clinical manifestations of DD/ID/epilepsy. Dmxl2 homozygous ko mice display embryonic lethality with heterozygous mice displaying macrocephaly and corpus callosum dysplasia (cited PMIDs: 25248098, 30735494) . Sources: Literature |
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| Early onset or syndromic epilepsy v1.425 | DMXL2 |
Konstantinos Varvagiannis gene: DMXL2 was added gene: DMXL2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: DMXL2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DMXL2 were set to 25248098; 30237576; 31688942; 30732576 Phenotypes for gene: DMXL2 were set to Epileptic encephalopathy, early infantile, 81, MIM 618663; ?Polyendocrine-polyneuropathy syndrome, MIM 616113 Penetrance for gene: DMXL2 were set to unknown Review for gene: DMXL2 was set to GREEN Added comment: This gene can be considered for inclusion in both ID and epilepsy panels probably with green (ID and epilepsy with >=4 relevant individuals/families/variants and >=2 studies, role of the protein, effect of variants in most cases demonstrated, phenotypic similarities with other disorders affecting autophagy, some evidence from animal models, etc) or amber rating. Rare heterozygous variants disrupting DMXL2 (intragenic losses/gains, SNVs, CNVs affecting also additional genes) have been reported in individuals with variable neurodevelopmental disorders (ASD and ID) or psychiatric phenotypes [Costain et al. 2019 - PMID: 30732576 - summarized in Table 1]. (Highly) variable expressivity and possibly incomplete penetrance were proposed in the respective study. As a result evidence for ID/seizures due to monoallelic variants appears to be relatively limited. DD, ID and (probably) epilepsy appear however to be constant features in several individuals with biallelic pathogenic variants as summarized in the studies below. OMIM recently added a relevant entry with the DMXL2-associated phenotypes being the following: - Epileptic encephalopathy, early infantile, 81; EIEE81 - 618663 (AD) [based on refs 2,3] - ?Deafness, autosomal dominant 71 - 617605 (AD) [DD/ID/seizures are not part of the phenotype] - ?Polyendocrine-polyneuropathy syndrome - 616113 (AR) [based on ref1] DMXL2 is not associated with any phenotype in G2P. In SysID it is listed as a candidate ID gene based on the report by Tata et al (ref1). This gene is included in some gene panels for ID. [1] Tata el al. (2014 - PMID: 25248098) reported on 3 sibs born to consanguineous Senegalese parents, presenting with a progressive endocrine and neurodevelopmental disorder. Features incl. incomplete puberty, central hypothyroidism, abnormal glucose regulation, moderate ID (3/3) and peripheral polyneuropathy. Seizures were not part of the phenotype. Linkage analysis suggested 2 candidate regions on chromosomes 13 and 15 with a LOD score of 2.5. High throughput sequencing of genes within these regions (~500) in an affected member and parent revealed a 15 bp in-frame deletion of DMXL2 (NM_015263.4:c.5827_5841del / p.Asp1943_Ser1947del). Sanger sequencing of other affected and unaffected members supported AR inheritance. RT-qPCR demonstrated that DMXL2 mRNA levels in blood lymphocytes were significantly lower in homozygous patients compared to heterozygous or wt family members or controls. The authors demonstrated that the encoded protein (rabconnectin-3a) is a synaptic protein (expressed in exocytosis vesicles) at the ends of axons of GnRH producing neurons. Neuron-specific deletion of one allele in mice resulted in delayed puberty and very low fertility. Adult mice had lower number of GnRH neurons in hypothalamus. siRNA-mediated downregulation of Dmxl2 expression in an insulin-secreting cell line resulted in only slight insulin secretion in response to augmenting concentrations of glucose, providing evidence of involvement of the protein in control of regulated insulin secretion. ----------- [2] Maddirevula et al. (2019 - PMID: 30237576) reported briefly on a 36 months old boy, born to consanguineous parents, homozygous for a frameshift DMXL2 variant [individual 17-3220 | NM_001174117.1:c.4349_4350insTTACATGA or p.(Glu1450Aspfs*23)]. Features included focal seizures (onset at the age of 3m) with subsequent global DD, absent eye contact, cerebral atrophy and macrocephaly. This individual was identified following re-evaluation of exome data in a database of ~1550 exomes specifically for homozygous variants that would have been classified earlier as LP/P if the respective gene had sufficient evidence for association with a disorder. The family was not reported to have other affected members. As the authors noted, the boy was not known to have the multi-endocrine abnormalities reported by Tata et al. There are no additional information provided (eg. on confirmation of variants, etc). ----------- [3] Esposito et al. (2019 - PMID: 31688942) report on 3 sibling pairs (all 3 families unrelated) with biallelic DMXL2 mutations and summarize previous evidence on the gene and the DMXL2-related phenotypes. All presented a highly similar phenotype of Ohtahara syndrome (seizures with onset in the first days of life, tonic/myoclonic/occasionaly focal, burst-suppression upon EEG), profound DD/ID, quadriparesis, sensorineural hearing loss and presence of dysmorphic features. Sibs from 2 families presented evidence of peripheral polyneuropathy. Early brain MRIs revealed thin CC and hypomyelination in all, with later scans suggestive of gray and white matter shrinkage with leukoencephalopathy. None achieved developmental skills following birth with 5/6 deceased by the age of 9 years. Exome sequencing revealed biallelic DMXL2 variants in all, with compatible parental segregation studies (NM_015263.3): - Fam1 (2 sibs) : c.5135C>T (p.Ala1712Val) in trans with c.4478C>G (p.Ser1493*) - Fam2 (2 sibs) : homozygosity for c.4478C>A (p.Ser1493*) - Fam3 (2 sibs) : homozygosity for c.7518-1G>A Heterozygous parents (aged 39-59) did not exhibit hearing impairment [report of a single multigenerational family by Chen et al (2017 - PMID: 27657680) where a heterozygous missense variant segregated with hearing loss - respective OMIM entry: ?Deafness, autosomal dominant 71 - 617605]. In patients' fibroblasts, effect of the variants on mRNA/protein expression was demonstrated with mRNA expressed only in a patient from family 1, and degraded/absent for the 2 stopgain SNVs affecting codon 1493. Skipping of ex31 leading to frameshift/introduction of a PTC was shown for the splice variant (p.Trp2508Argfs*4 secondary to c.7518-1G>A). Protein was also absent upon western-blot. DMXL2 encodes a vesicular protein, DmX-Like protein 2 or rabconnectin-3a (cited Tata et al). The gene is expressed in brain ( https://www.gtexportal.org/home/gene/DMXL2 ). As Esposito et al comment, it is known to regulate the trafficking and activity of v-ATPase the latter having a role in acidifying intracellular organelles and promoting endosomal maturation (cited PMIDs : 25248098, 19758563, 22875945, 24802872). In line with this, staining of patients' fibroblasts using the acidotropic dye LysoTracker demonstrated increased signal, reversed by re-expression of DMXL2 protein. Overall an acidic shift in pH with impairment of lysosomal structures and function was suggested. The authors provided additional evidence for altered lysosomal function and associated autophagy with accumulation of autophagy receptors (eg p62) and substrates (polyubiquitinated proteins). Vacuolization and accumulation of atypical fusion-like structures was shown upon ultrastractural analysis. shRNA-mediated downregulation/silencing of Dmxl2 in mouse hippocampal neurons resulted also in altered lysosomal structures and defective autophagy. The neurons exhibited impaired neurite elongation and synapse formation. The authors suggest similarities with Vici syndrome, where biallelic EPG5 mutations result in autophagic defects and clinical manifestations of DD/ID/epilepsy. Dmxl2 homozygous ko mice display embryonic lethality with heterozygous mice displaying macrocephaly and corpus callosum dysplasia (cited PMIDs: 25248098, 30735494) . Sources: Literature |
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| Intellectual disability v2.1102 | DMXL2 | Konstantinos Varvagiannis reviewed gene: DMXL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25248098, 30237576, 31688942; Phenotypes: Epileptic encephalopathy, early infantile, 81, MIM 618663, ?Polyendocrine-polyneuropathy syndrome, MIM 616113; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.244 | RAD21 | Eleanor Williams changed review comment from: Comment on list classification: Promoted from red to amber. 2 cases reported in OMIM with SNV and short stature (1 case) and limb defects (2 cases). ; to: Comment on list classification: Promoted from red to amber. 2 cases reported in OMIM with SNV and short stature (1 case) and limb defects. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.244 | RAD21 | Eleanor Williams changed review comment from: Comment on list classification: Promoted from red to amber. 2 cases reported in OMIM with SNV and short stature (1 case) and limb defects (2 cases). Other cases of deletions covering this gene and a similar phenotype are also reported.; to: Comment on list classification: Promoted from red to amber. 2 cases reported in OMIM with SNV and short stature (1 case) and limb defects (2 cases). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.244 | RAD21 |
Eleanor Williams changed review comment from: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. Clinical features listed include short stature and limb defects. OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short (1 patients) and thin (1 patient) fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified. Other publications with patients with Cornelia de Lange and RAD21 variants: PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay. PMID: 24378232 - Minor et al., 2014 - 2 patients with atypic Cornelia de Lange. Patient 1 - in frame deletion of exon 13 - presented with developmental delay, hypospadias, inguinal hernia and dysmorphic features, mild 5th finger clinodactyly. This deletion was found to be inherited from the mother who had a history of melanoma and other unspecified medical problems. Patient 2 - c.592_593dup frameshift mutation - presented with developmental delay, characteristic facial features, hirsutism, and hand and feet anomalies (clinodactyly, syndactyly). The mother had the same frameshift mutation showing incomplete penetrance. PMID: 27882533 - Boyle et al., 2017 - patient with microcephaly and classical CdLS facial features with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance. PMID: 27620904 - Martinez et al., 2017 - 92 patients recruited with syndromic intellectual disability. 1 patient identified with a variant in RAD21. A diagnosis of CdLS was made. ; to: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. Clinical features listed include short stature and limb defects. OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short fingers (1 patient) and thin fingers (1 patient) and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21, aswell as other genes, were reported. Other publications with patients with Cornelia de Lange and RAD21 variants but no major skeletal phenotype: PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay. PMID: 24378232 - Minor et al., 2014 - 2 patients with atypic Cornelia de Lange. Patient 1 - in frame deletion of exon 13 - presented with developmental delay, hypospadias, inguinal hernia and dysmorphic features, mild 5th finger clinodactyly. This deletion was found to be inherited from the mother who had a history of melanoma and other unspecified medical problems. Patient 2 - c.592_593dup frameshift mutation - presented with developmental delay, characteristic facial features, hirsutism, and hand and feet anomalies (clinodactyly, syndactyly). The mother had the same frameshift mutation showing incomplete penetrance. PMID: 27882533 - Boyle et al., 2017 - patient with microcephaly and classical CdLS facial features with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance. PMID: 27620904 - Martinez et al., 2017 - 92 patients recruited with syndromic intellectual disability. 1 patient identified with a variant in RAD21. A diagnosis of CdLS was made. |
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| Skeletal dysplasia v1.244 | TWIST2 | Eleanor Williams changed review comment from: Comment on list classification: Removing this gene from the panel as the OMIM phenotypes to not have a clear skeletal phenotype.; to: Comment on list classification: Removing this gene from the panel as the OMIM associated diseases do not have a clear skeletal phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.21 | PIK3C2A | Eleanor Williams Classified gene: PIK3C2A as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.21 | PIK3C2A | Eleanor Williams Added comment: Comment on list classification: Rating green as 3 cases have been reported with skeletal involvement. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.21 | PIK3C2A | Eleanor Williams Gene: pik3c2a has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.20 | PIK3C2A |
Eleanor Williams gene: PIK3C2A was added gene: PIK3C2A was added to Skeletal ciliopathies. Sources: Literature Mode of inheritance for gene: PIK3C2A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIK3C2A were set to 31034465 Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome 618440 Added comment: Associated with Oculoskeletodental syndrome #618440 (AR) in OMIM. This is based on evidence from PMID: 31034465 - Tiosano et al 2019 - report 5 individuals from 3 unrelated consanguineous families with a similar set of clinical features including dysmorphic facial features, short stature, skeletal and neurological abnormalities, and cataracts. The skeletal findings included "scoliosis, delayed bone age, diminished ossification of femoral heads, cervical lordosis, shortened fifth digits with mild metaphyseal dysplasia and clinodactyly". Homozygous loss-of-function mutations in PIK3C2A were identified in each family. The authors found that PIK3C2A is critical for the formation of cilia and therefore is appropriate for inclusion on the skeletal ciliopathy panel. Sources: Literature |
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| Skeletal dysplasia v1.244 | SULF1 | Eleanor Williams changed review comment from: Comment on list classification: Changing rating back to red. In all reported cases associated with deletions and patients with Mesomelia-synostoses syndrome both SULF1 and SLC05A1 are deleted, so better to represent this as a region.; to: Comment on list classification: Changing rating back to red. In all reported cases associated with deletions and patients with Mesomelia-synostoses syndrome both SULF1 and SLCO5A1 are deleted, so better to represent this as a region. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.244 | SLCO5A1 | Eleanor Williams Classified gene: SLCO5A1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.244 | SLCO5A1 | Eleanor Williams Added comment: Comment on list classification: Changing rating back to red. In all reported cases associated with deletions and patients with Mesomelia-synostoses syndrome both SULF1 and SLCO5A1 are deleted, so better to represent this as a region | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.244 | SLCO5A1 | Eleanor Williams Gene: slco5a1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.243 | SULF1 | Eleanor Williams Classified gene: SULF1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.243 | SULF1 | Eleanor Williams Added comment: Comment on list classification: Changing rating back to red. In all reported cases associated with deletions and patients with Mesomelia-synostoses syndrome both SULF1 and SLC05A1 are deleted, so better to represent this as a region. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.243 | SULF1 | Eleanor Williams Gene: sulf1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.242 | SULF1 |
Eleanor Williams changed review comment from: Not associated with any phenotype in OMIM or Gene2Phenotype. PMID: 20602915 - Isidor et al 2010 - using whole-genome oligonucleotide array CGH, they identified an interstitial deletion at 8q13 in 5 patients from 4 unrelated families with Mesomelia-synostoses syndrome. The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1 and SLCO5A1. Breakpoint sequence analyses performed in two families showed nonrecurrent deletions. Codeletion of SULF1 and SLCO5A1was found in all patients, suggesting that haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS. PMID: 28328141 - Kohmoto et al 2017 - report the first Japanese case with MSS diagnosed by detecting an 8q13 deletion (581 Kb monoallelic deletion) that resulted from a unique, distant L1s‐mediated unequal NAHR event, which is different from the possible mechanisms proposed in previously reported cases. The deletion encompasses SULF1, SLCO5A1, and LINC01603. The size of the 8q13 deletion was different from those of any of the four reported deletions responsible for MSS (Isidor et al., 2010). The deletion could not be confirmed as de novo because of the unavailability of parental DNA. PMID: 30450550 - Dardis et al 2019 - describe the first patient affected by MSS without the previously described 8q13 deletions. Patient is an 8‐year‐old 46,XY male presenting the radiological and clinical hallmarks of MSS. Microdeletions of SULF1 and SLCO5A1 genes at 8q13 were absent. Sequencing of SULF1 and SLCO5A1 found 4 polymorphisms but no pathogenic mutations. However, it was found that there was monoallelic expression of SULF1 in the patient's cells, likely leading to SULF1 haploinsufficiency. There may be either a deletion of a portion of SULF1 gene not detectable by PCR or CGH array or mutations or epigenetic alterations in sequences that contribute to the regulation of SULF1 expression. Summary, there are 5 cases where deletions covering both SULF1 and SLCO5A1 are found in patients with MSS. There is one case of MSS in a patient with no detectable deletions of SULF1 and SLCO5A1, but with monoallelic expression of SULF1. There is no current regions curated by ClinGen that cover these genes.; to: Not associated with any phenotype in OMIM or Gene2Phenotype. PMID: 20602915 - Isidor et al 2010 - using whole-genome oligonucleotide array CGH, they identified an interstitial deletion at 8q13 in 5 patients from 4 unrelated families with Mesomelia-synostoses syndrome. The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1 and SLCO5A1. Breakpoint sequence analyses performed in two families showed nonrecurrent deletions. Codeletion of SULF1 and SLCO5A1was found in all patients, suggesting that haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS. PMID: 28328141 - Kohmoto et al 2017 - report the first Japanese case with MSS diagnosed by detecting an 8q13 deletion (581 Kb monoallelic deletion) that resulted from a unique, distant L1s‐mediated unequal NAHR event, which is different from the possible mechanisms proposed in previously reported cases. The deletion encompasses SULF1, SLCO5A1, and LINC01603. The size of the 8q13 deletion was different from those of any of the four reported deletions responsible for MSS (Isidor et al., 2010). The deletion could not be confirmed as de novo because of the unavailability of parental DNA. PMID: 30450550 - Dardis et al 2019 - describe the first patient affected by MSS without the previously described 8q13 deletions. Patient is an 8‐year‐old 46,XY male presenting the radiological and clinical hallmarks of MSS. Microdeletions of SULF1 and SLCO5A1 genes at 8q13 were absent. Sequencing of SULF1 and SLCO5A1 found 4 polymorphisms but no pathogenic mutations. However, it was found that there was monoallelic expression of SULF1 in the patient's cells, likely leading to SULF1 haploinsufficiency. There may be either a deletion of a portion of SULF1 gene not detectable by PCR or CGH array or mutations or epigenetic alterations in sequences that contribute to the regulation of SULF1 expression. Summary, there are 5 cases where deletions covering both SULF1 and SLCO5A1 are found in patients with MSS. There is one case of MSS in a patient with no detectable deletions of SULF1 and SLCO5A1, but with monoallelic expression of SULF1. There are no current regions curated by ClinGen that cover these genes. |
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| Limb disorders v1.65 | TGDS | Eleanor Williams Classified gene: TGDS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.65 | TGDS | Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. More than 3 cases reported with variants in this gene and limb defects. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.65 | TGDS | Eleanor Williams Gene: tgds has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.242 | TGDS |
Eleanor Williams changed review comment from: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM. PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation ; to: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM. PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation. 1 patient showed short toes, short humeri, short femora, 3 had clinodactyly V and 1 had brachymetacarpia and scoliosis. PMID: 26366375 - Pferdehirt et al 2015 - describe a 12-month-old male with molecularly confirmed Catel-Manzke syndrome who presented with Pierre Robin sequence (but without cleft palate) and hyperphalangy. This patient is on the severe end of the phenotypic spectrum, presenting with respiratory complications and failure to thrive. He has a homozygous p.Ala100Ser pathogenic variant. Both parents are heterozygous for this variant. PMID: 28422407 - Schoner et al 2017 - report on a fetus with severe heart defect, nuchal edema, talipes, Pierre-Robin sequence, and bilateral deviation and clinodactyly of the index and middle fingers. Postmortem radiographs showed hypoplasia and V-shaped displacement of the second and third proximal phalanges of both hands as well as hypoplasia of the first metatarsals and the phalangeal bones of the halluces. Two compound heterozygous mutations in TGDS were found: c.298G>T; p.(Ala100Ser) and c.895G>A; p.(Asp299Asn), located in the predicted substrate binding site of TGDS. Analyses of the parents’ blood DNA confirmed biparental inheritance. |
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| Limb disorders v1.64 | TGDS |
Eleanor Williams changed review comment from: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM. PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation. 1 patient showed short toes, short humeri, short femora, 3 had clinodactyly V and 1 had brachymetacarpia and scoliosis. PMID: 26366375 - Pferdehirt et al 2015 - describe a 12-month-old male with molecularly confirmed Catel-Manzke syndrome who presented with Pierre Robin sequence (but without cleft palate) and hyperphalangy. This patient is on the severe end of the phenotypic spectrum, presenting with respiratory complications and failure to thrive. He has a homozygous p.Ala100Ser pathogenic variant. Both parents are heterozygous for this variant. PMID: 28422407 - Schoner et al 2017 - report on a fetus with severe heart defect, nuchal edema, talipes, Pierre-Robin sequence, and bilateral deviation and clinodactyly of the index and middle fingers. Postmortem radiographs showed hypoplasia and V-shaped displacement of the second and third proximal phalanges of both hands as well as hypoplasia of the first metatarsals and the phalangeal bones of the halluces. Two compound heterozygous mutations in TGDS were found: c.298G>T; p.(Ala100Ser) and c.895G>A; p.(Asp299Asn), located in the predicted substrate binding site of TGDS. ; to: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM. PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation. 1 patient showed short toes, short humeri, short femora, 3 had clinodactyly V and 1 had brachymetacarpia and scoliosis. PMID: 26366375 - Pferdehirt et al 2015 - describe a 12-month-old male with molecularly confirmed Catel-Manzke syndrome who presented with Pierre Robin sequence (but without cleft palate) and hyperphalangy. This patient is on the severe end of the phenotypic spectrum, presenting with respiratory complications and failure to thrive. He has a homozygous p.Ala100Ser pathogenic variant. Both parents are heterozygous for this variant. PMID: 28422407 - Schoner et al 2017 - report on a fetus with severe heart defect, nuchal edema, talipes, Pierre-Robin sequence, and bilateral deviation and clinodactyly of the index and middle fingers. Postmortem radiographs showed hypoplasia and V-shaped displacement of the second and third proximal phalanges of both hands as well as hypoplasia of the first metatarsals and the phalangeal bones of the halluces. Two compound heterozygous mutations in TGDS were found: c.298G>T; p.(Ala100Ser) and c.895G>A; p.(Asp299Asn), located in the predicted substrate binding site of TGDS. Analyses of the parents’ blood DNA confirmed biparental inheritance. |
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| Limb disorders v1.64 | TGDS |
Eleanor Williams changed review comment from: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM. PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation Sources: Literature; to: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM. PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation. 1 patient showed short toes, short humeri, short femora, 3 had clinodactyly V and 1 had brachymetacarpia and scoliosis. PMID: 26366375 - Pferdehirt et al 2015 - describe a 12-month-old male with molecularly confirmed Catel-Manzke syndrome who presented with Pierre Robin sequence (but without cleft palate) and hyperphalangy. This patient is on the severe end of the phenotypic spectrum, presenting with respiratory complications and failure to thrive. He has a homozygous p.Ala100Ser pathogenic variant. Both parents are heterozygous for this variant. PMID: 28422407 - Schoner et al 2017 - report on a fetus with severe heart defect, nuchal edema, talipes, Pierre-Robin sequence, and bilateral deviation and clinodactyly of the index and middle fingers. Postmortem radiographs showed hypoplasia and V-shaped displacement of the second and third proximal phalanges of both hands as well as hypoplasia of the first metatarsals and the phalangeal bones of the halluces. Two compound heterozygous mutations in TGDS were found: c.298G>T; p.(Ala100Ser) and c.895G>A; p.(Asp299Asn), located in the predicted substrate binding site of TGDS. |
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| Early onset or syndromic epilepsy v1.425 | ALG8 | Rebecca Foulger commented on gene: ALG8: PMID:19688606 (Vesela et al., 2009) present a girl with neonatal onset of CDG. Seizures were present from the first day and the girl died age 2 months from progressive oedema, bleeding and cardio-respiratory insufficiency. She had compound het variants in ALG8 (p.T47P and p.R364X). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.425 | ALG8 | Rebecca Foulger commented on gene: ALG8: PMID:23430830 (Millon et al., 2011) report 2 siblings with a congenital glycosylation disorder. Their clinical presentation included seizures. The authors could not identify the genetic deficiency in these patients yet. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.425 | ALG8 | Rebecca Foulger commented on gene: ALG8: 26066342 (Hock et al., 2015) describe 3 new patients with ALG8-CDG, provide an update on 2 previous patients and summarise 10 previous patients. The 15 patients total included 4 pairs of siblings. Brain involvement (psychomotor disability or seizures or ataxia or structural anomalies) were seen in 12/13 patients. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.425 | FLNA | Alison Callaway reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia v1.202 | CACNA2D2 |
Zerin Hyder gene: CACNA2D2 was added gene: CACNA2D2 was added to Hereditary ataxia. Sources: Other Mode of inheritance for gene: CACNA2D2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CACNA2D2 were set to PMID: 30410802, PMID: 31402629, PMID: 24358150, PMID: 23339110, PMID: 29997391; PMID : 14660671; PMID: 15331424 Phenotypes for gene: CACNA2D2 were set to epilepsy; ataxia; developmental delay; cerebellar atrophy Penetrance for gene: CACNA2D2 were set to unknown Review for gene: CACNA2D2 was set to GREEN Added comment: CACNA2D2 biallelic variants are associated with cerebellar atrophy with seizures and variable developmental delay (6 publications of affected families in the literature). Most patients also have onset of severe refractory seizures in the first year of life and show global developmental delay, compatible with epileptic encephalopathy (summary by Edvardson et al., 2013). However, at least 1 patient with normal cognitive development and only 1 febrile seizure has been reported (Valence et al., 2019), suggesting significant clinical variability of this disorder (OMIM 618501). Mouse models including The 'ducky' mouse model (due to biallelic Cacna2d2 mutations) presented with absence epilepsy, spike-wave seizures and ataxia. Dysgenesis of the cerebellum is among the neuropathological findings (Brodbeck et al. (2002)). Mutations of the same gene in two other mouse models shows an association with ataxic gait, seizure susceptibility and cerebellar anomalies/degeneration. Multiple submissions to ClinVar of biallelic variants rated as pathogenic for epileptic encephalopathy. Suggest update to green on panel. Sources: Other |
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| Early onset or syndromic epilepsy v1.425 | CACNA2D2 | Zerin Hyder reviewed gene: CACNA2D2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30410802, PMID: 31402629, PMID: 24358150, PMID: 23339110, PMID: 29997391; Phenotypes: epilepsy, ataxia, developmental delay, cerebellar atrophy; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.425 | SLC6A19 | Rebecca Foulger Phenotypes for gene: SLC6A19 were changed from to Hartnup disorder, 234500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.424 | SLC6A19 | Rebecca Foulger Publications for gene: SLC6A19 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.423 | SLC6A19 | Rebecca Foulger commented on gene: SLC6A19: PMID:20399395 (Cheon et al 2010) report a Korean boy age 8 years and 5 months with Hartnup disorder. He had seizures, ADHD and mental retardation. Genetic analysis revealed novel compound het variants in SLC6A19: p.Thr596fsX73 and p.Ser303Leu. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.64 | TGDS |
Eleanor Williams gene: TGDS was added gene: TGDS was added to Limb disorders. Sources: Literature Mode of inheritance for gene: TGDS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TGDS were set to 25480037 Phenotypes for gene: TGDS were set to Catel-Manzke syndrome 616145 Review for gene: TGDS was set to GREEN Added comment: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM. PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation Sources: Literature |
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| Skeletal dysplasia v1.242 | TGDS | Eleanor Williams Publications for gene: TGDS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.241 | TGDS | Eleanor Williams Mode of inheritance for gene: TGDS was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.240 | TGDS |
Eleanor Williams changed review comment from: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM. PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation In 7 patients with Catel-Manzke syndrome (616145), Ehmke et al. (2014) identified homozygosity or compound heterozygosity for mutations in the TGDS gene; to: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM. PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation |
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| Skeletal dysplasia v1.240 | SLCO5A1 | Eleanor Williams Tag currently-ngs-unreportable was removed from gene: SLCO5A1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.240 | SULF1 | Eleanor Williams Tag currently-ngs-unreportable was removed from gene: SULF1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.352 | SCO2 | Rebecca Foulger commented on gene: SCO2: PMID:18924171 (Verdijk et al, 2008) report the first prenatal diagnosis of a compound heterozygous SCO2 variant in the literature. The sibling died of fatal infantile cardioencephalomyopathy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.240 | SULF1 | Eleanor Williams Classified gene: SULF1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.240 | SULF1 | Eleanor Williams Added comment: Comment on list classification: Changing rating to green. Deletions covering this gene will be reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.240 | SULF1 | Eleanor Williams Gene: sulf1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.239 | SLCO5A1 | Eleanor Williams Classified gene: SLCO5A1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.239 | SLCO5A1 | Eleanor Williams Added comment: Comment on list classification: Changing rating to green. Deletions covering this gene will be reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.239 | SLCO5A1 | Eleanor Williams Gene: slco5a1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.352 | SCO2 | Rebecca Foulger Publications for gene: SCO2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.423 | SCO2 | Rebecca Foulger commented on gene: SCO2: PMID:18924171 (Verdijk et al, 2008) report compound het SOC2 variants (E140K and W36X) in 2 siblings with fatal infantile cardioencephalomyopathy. The index patient had convulsions age 1 day and died of heart failure age 25 days. The sibling fetus was terminated at 23 weeks following genetic testing. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.238 | P4HB | Eleanor Williams Mode of pathogenicity for gene: P4HB was changed from Other to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.237 | P4HB | Eleanor Williams Added comment: Comment on mode of pathogenicity: 1 missense variant reported to date + deletion of several exons. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.237 | P4HB | Eleanor Williams Mode of pathogenicity for gene: P4HB was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.236 | P4HB | Eleanor Williams Classified gene: P4HB as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.236 | P4HB |
Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. > 3 cases. Including OI genes on this panel. |
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| Skeletal dysplasia v1.236 | P4HB | Eleanor Williams Gene: p4hb has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.423 | SCO2 | Rebecca Foulger commented on gene: SCO2: PMID:10749987 (Jaksch et al., 2000) report 10 patients with fatal hypertrophic cardiomyopathy from 9 families. Mutations in SCO2 (E140K, R171W) were found in 3 patients (2 unrelated families) all of whom had seizures: Table 1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.235 | MASP1 | Eleanor Williams Classified gene: MASP1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.235 | MASP1 | Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. >3 cases reported. Skeletal phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.235 | MASP1 | Eleanor Williams Gene: masp1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.234 | MASP1 | Eleanor Williams Mode of inheritance for gene: MASP1 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.233 | MASP1 |
Eleanor Williams commented on gene: MASP1: Associated with 3MC syndrome 1 #257920 (AR) in OMIM. Post natal growth retardation and radioulnar synostosis as well as craniosynostosis are listed as clinical features. 6 families and 5 variants in MASP1 reported in OMIM. COLEC11 associated with 3MC syndrome 2 is already green on the panel. |
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| Early onset or syndromic epilepsy v1.423 | SCO2 | Rebecca Foulger commented on gene: SCO2: PMID:10545952 (Papadopoulou et al 1999) identified variants in SCO2 in 3 unrelated infants with fatal cardioencephalomyopathy and COX deficiency. Patient 2 had focal epileptiform discharges on an EEG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.233 | MANBA | Eleanor Williams Tag watchlist tag was added to gene: MANBA. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.233 | MANBA | Eleanor Williams Classified gene: MANBA as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.233 | MANBA | Eleanor Williams Added comment: Comment on list classification: Only 1 family reported with a strong skeletal phenotype so rating amber for now. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.233 | MANBA | Eleanor Williams Gene: manba has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.232 | MANBA | Eleanor Williams Publications for gene: MANBA were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.231 | MANBA | Eleanor Williams Mode of inheritance for gene: MANBA was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.423 | SCO1 | Rebecca Foulger commented on gene: SCO1: PMID:22231385 (Honzik et al., 2012) summarise 461 patients with mitochondrial disorders. One patient had a variant in SCO1: seizures were not a feature (Table 2, Stiburek et al., 2009). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.423 | SCO1 | Rebecca Foulger changed review comment from: PMID:15023375 report an 8-week old infant who presented with neonatal seizures and limb malformations. There were multiple seizure types, including multifocal myoclonus, complex partial events and generalised tonic–clonic episodes. Treatment of seizures was of limited success. The specific defect seen in the patient was a complex IV deficiency. Although no known variants were identified, the clinical picture overlaps with the SCO1 presentation.; to: PMID:15023375 (Kurian et al., 2004) report an 8-week old infant who presented with neonatal seizures and limb malformations. There were multiple seizure types, including multifocal myoclonus, complex partial events and generalised tonic–clonic episodes. Treatment of seizures was of limited success. The specific defect seen in the patient was a complex IV deficiency. Although no known variants were identified, the clinical picture overlaps with the SCO1 presentation. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.230 | MANBA |
Eleanor Williams commented on gene: MANBA: Associated with Mannosidosis, beta #248510 (AR) in OMIM. No clear skeletal phenotype listed in the clinical features in OMIM. >3 cases reported with homozygous or compound het variants in OMIM. PMID: 2079835 - Kleijer et al 1990 - report a family with Mannosidosis in which a homozygous variant in the MANBA gene was later identified by Alkhayat et al. (1998). Some affected individuals showed scoliosis, one individual showed deformities of the thorax, lumbar hyperlordosis and nanism. PMID: 16401745 - Sedel et al 2006 - 1 case of boy with beta-mannosidase deficiency. No skeletal phenotype reported. PMID: 18980795 - Labauge et al 2009 - 1 case of boy with beta-mannosidase deficiency. No skeletal phenotype reported. |
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| Early onset or syndromic epilepsy v1.423 | SCO1 | Rebecca Foulger Publications for gene: SCO1 were set to 23878101; 11013136; 19295170 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.422 | SCO1 | Rebecca Foulger changed review comment from: PMID:23878101 (Leary et al., 2013) report compound het variants in SCO1 in a patient with fatal encephalopathy. The patient developed seizures age 4 months which were difficult to control. He died age 5 months (Supporting information).; to: PMID:23878101 (Leary et al., 2013) report compound het variants in SCO1 in a patient with fatal encephalopathy. The patient developed seizures age 4 months which were difficult to control. He died age 5 months (seizure information and extended clinical phenotype is the supporting information). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.422 | SCO1 | Rebecca Foulger commented on gene: SCO1: PMID:15023375 report an 8-week old infant who presented with neonatal seizures and limb malformations. There were multiple seizure types, including multifocal myoclonus, complex partial events and generalised tonic–clonic episodes. Treatment of seizures was of limited success. The specific defect seen in the patient was a complex IV deficiency. Although no known variants were identified, the clinical picture overlaps with the SCO1 presentation. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.422 | SCO1 | Rebecca Foulger commented on gene: SCO1: PMID:23878101 (Leary et al., 2013) report compound het variants in SCO1 in a patient with fatal encephalopathy. The patient developed seizures age 4 months which were difficult to control. He died age 5 months (Supporting information). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.422 | QDPR | Rebecca Foulger Phenotypes for gene: QDPR were changed from Hyperphenylalaninemia, BH4-deficient, C, 261630 to Hyperphenylalaninemia, BH4-deficient, C, 261630; DHPR deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.421 | QDPR | Rebecca Foulger Publications for gene: QDPR were set to 9341885; 26006720 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.420 | QDPR | Rebecca Foulger commented on gene: QDPR: Seizures listed in the OMIM Clinical synopsis for 'Hyperphenylalaninemia, BH4-deficient, C' (MIM:261630). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.420 | QDPR | Rebecca Foulger commented on gene: QDPR: Ikeda et al. (1997, PMID:9341885) report a Japanese boy with hyperphenylalaninemia and a splicing error variant in QDPR. He was the offspring of first-cousin parents. The patient showed intractable seizures and developmental delay. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.420 | PRODH | Rebecca Foulger Publications for gene: PRODH were set to 12217952 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.419 | PRODH | Rebecca Foulger commented on gene: PRODH: PMID:17412540 (Afenjar et al 2007) report 4 unrelated children and biallelic variants in PRODH. The authors note that 4 previous patients had been reported (Jacquet et al, 2002, 2003 and Raux et al 2007) and of the 8 total patients, 5 had epilepsy (plus febrile case), often severe with status epilepticus. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.419 | PRODH | Rebecca Foulger commented on gene: PRODH: PMID:18197084 (Di Rosa et al., 2008) screened 4 unrelated Italian children all of whom presented with epilepsy and ID, and compound het/homozygous variants in PRODH. Functional tests to confirm the pathogenicity were not performed. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.419 | PRODH | Rebecca Foulger Publications for gene: PRODH were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.418 | PEX1 | Rebecca Foulger commented on gene: PEX1: PMID:16141001 (Rosewich et al 2005) studied 33 patients with PEX1 variants. Seizures are a feature in Table 3 for 6 patients. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.418 | PEX1 | Rebecca Foulger Publications for gene: PEX1 were set to 12402331; 26387595; 9398847 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.417 | PEX1 | Rebecca Foulger commented on gene: PEX1: PMID:15098231 (Poll-The BT et al 2004) surveyed 31 patients with a generalized peroxisomal disorder from 27 families. 7/31 patients (23%) developed seizures from 0 - 2.7 years. Most patients (60-70%) had variants in the PEX1 gene. Most frequent variants include G843D and frameshift c.2097insT. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.417 | PEX1 | Rebecca Foulger commented on gene: PEX1: PMID:15301838 (Michelakakis et al, 2004) decribe a female patient of healthy unrelated patients. Her diagnosis of Leber congenital amaurosis was subsequently demonstrated to be a PEX1 defect. Myoclonic seizures began age 2. The patient is heterozygous for G843D variant and an additional second variant that is not yet identified. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.417 | PEX1 | Rebecca Foulger commented on gene: PEX1: PMID:28432012 (Ge et al., 2017) report 2 Chinese newborns with Zellweger phenotypes and compound het variants in PEX1 (Arg577Thrfs*15 and Asn830Thrfx*61). Although the authors note that seizures are in the clinical spectrum of ZS patients, seizures were not reported for the Chinese newborns. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.417 | PEX1 | Rebecca Foulger commented on gene: PEX1: PMID:21844578 (Cho et al., 2011) report a Korean patient who was compound het for variants in the PEX1 gene (p.H678QfsX3 and p.R949W) inherited from the parents. He had typical features of ZS including seizures (starting 4 days old), dysmorphic face and a poor suck. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.417 | MTR | Rebecca Foulger commented on gene: MTR: PMID:28666289 (Komulainen-Ebrahim et al., 2017) describe a homozygous MTR p.P1173L variant in a patient with drug-resistant seizures associated with hyperhomocysteinemia and hypomethioninemia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.417 | MTR | Rebecca Foulger commented on gene: MTR: PMID:9683607 (Wilson et al., 1998) report 3 cblG patients, including 2 siblings who presented with neonatal seizures. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.417 | MTR | Rebecca Foulger commented on gene: MTR: PMID:25526710 (Huemer et al., 2015) summarise clinical features of 13 patients with the cblG defect (caused by defects in MTR): 5/13 had seizures. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.417 | IDH2 | Rebecca Foulger commented on gene: IDH2: A number of papers note that IDH1 and IDH2 variants have an established association with preoperative seizures in patients with grade II-IV diffuse gliomas (PMID:29172136, 29288860, 22217666). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.417 | IDH2 | Rebecca Foulger Publications for gene: IDH2 were set to 20847235 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.416 | IDH2 | Rebecca Foulger commented on gene: IDH2: PMID:24049096 (Nota et al., 2013) report 3 cases, with seizures reported in 2/3. Case 2 was a 9 year old Caucasian girl with tonic-clonic seizures and mosaic IDH2 variants. Case 3 was a Caucasian girl with seizures age 3 months- her seizures responded well to anticonvulsants. The patient died from sudden cardiac arrest age 8, and was found to have a heterozygous IDH2 c.419G>A variant. Germline mosaicism in the mother was suggested to explain the inheritance pattern in this family. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.416 | HLCS | Rebecca Foulger commented on gene: HLCS: PMID:27114915 (Donti et al., 2016) describe a cohort of 5 patients. Case 5 had focal seizures age 5 months which have continued since. He has compound het variants in HLCS (N570K and c.1519+5G>A). The authors note that the phenotypic spectrum of HCLS is broad, from intractable seizures and ID to normal growth and development. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.416 | GSS | Rebecca Foulger Publications for gene: GSS were set to 26984560 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.415 | GSS | Rebecca Foulger commented on gene: GSS: PMID:26669244 (Gunduz et al., 2016) report 4 patients with GS deficiency. Case I and Case IV had seizures noted together with homozygous variants (splicing variant in I and p.R125H in IV): Table 1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.415 | GSS | Rebecca Foulger commented on gene: GSS: Seizures are recorded in OMIM Clinical synopsis for MIM:266130 based on Marstein et al., 1976 (no PubMed). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.415 | GSS | Rebecca Foulger commented on gene: GSS: PMID:15990954 (Njallson et al 2005) summarise the phenotypes of patients with glutathione synthetase deficiency, but don't mention seizures or epilepsy (as noted in review by Tracy Lester). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.415 | GSS | Rebecca Foulger commented on gene: GSS: PMID:11445798 (Ristoff et al,. 2001) examined 28 patients with Glutathione synthetase deficiency (GSSD). Diagnosis was based on metabolic tests. 16/28 had neurological symptoms such as seizures/psychomotor retardation. In 16 patients with severe GS deficiency, 7 had seizures. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.415 | GSS | Rebecca Foulger commented on gene: GSS: PMID:26984560 (Atwal et al. 2016) present a 19 year old female with Glutathione synthetase deficiency (GSSD). She was diagnosed with a mild seizure disorder age 10, and treated with the antiepileptic lamotrigine, which was discontinued once she was seizure free for 5 years. The authors note it is possible her seizures were unrelated to the underlying GSSD. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.415 | GSS | Rebecca Foulger Publications for gene: GSS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.414 | GLYCTK | Rebecca Foulger Publications for gene: GLYCTK were set to 3588091; 30637540; 28462797; 20949620 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.413 | GLYCTK | Rebecca Foulger Publications for gene: GLYCTK were set to 3588091 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.412 | GLYCTK | Rebecca Foulger commented on gene: GLYCTK: PMID:30637540 (Zehavi et al., 2019) report a male from a consanguineous Arab family with intractable seizures and a homozygous missense pathogenic variant in GLYCTK (p.Leu152Pro). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.412 | GLYCTK | Rebecca Foulger commented on gene: GLYCTK: PMID:28462797 (Swanson et al., 2017) reviewed the Serbian patient from Sass et al., 2010. In addition to p.Phe483SerfsX2 variant in GLYCTK, the patient had an additional Ser117Leu variant in AMT highlighting the co-occurence of two metabolic conditions (D-glyceric aciduria and nonketotic hyperglycinemia). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.412 | GLYCTK |
Rebecca Foulger commented on gene: GLYCTK: PMID:20949620 (Sass et al., 2010) report 3 patients of Serbian, Mexican and Turkish origin, including the original 1974 (Serbian) patient. All had homozygous variant in GLYTCK: Patient A was a Serbian boy with generalized seizures beginning age 8 weeks (p.Phe483SerfsX2 variant). Patient B was a Mexican girl with focal clonic seizures and a Phe493Cys variant. Patient C was a Turkish boy where seizures were not noted (p.Leu520CysfsX108 variant). |
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| Early onset or syndromic epilepsy v1.412 | GFM1 | Rebecca Foulger Publications for gene: GFM1 were set to 25852744; 26937387; 28216230; 23430926; 21986555 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.411 | GFM1 | Rebecca Foulger commented on gene: GFM1: PMID:28216230 (Simon et al., 2017) report 2 brothers with compound het variants in GFM1 (maternally-inherited p.Arg250Trp and paternally-inherited p.Gly230_231Glnins19). The younger brother (P1) developed seizures by 4.5 months, characterised as infantile spasms. He has remained seizure free on treatment with topiramate. No seizures were noted for the brother who died age 10 months from multiple organ failure. The authors suggest additional modifier genes may be responsible for the different in severity between the brothers. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.411 | GFM1 | Rebecca Foulger commented on gene: GFM1: PMID:26937387 (Ravn et al., 2015) describe 3 patients with novel GFM1 variants. Patient 3 (a girl of non-consanguineous parents) had epileptic seizures beginning at 2 months old. She died at 3 months during a febrile episode. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.411 | GFM1 | Rebecca Foulger commented on gene: GFM1: PMID:21986555. Galmiche et al., 2012 report two unrelated patients with homozygous GFM1 variants (R671C). The parents were both heterozygous for this variant For the first patient (an Algerian boy from consanguineous parents), no clinical seizures were noted but EEG showed burst of multifocal spikes. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.411 | GFM1 | Rebecca Foulger commented on gene: GFM1: PMID:25852744. Brito et al., 2015 report an infant born to unrelated Caucasian parents with seizures amongst her phenotype (starting age 7 months) and compound het variants in GFM1 (Gly469Valfs*84 and Arg671Cys). The authors summarise clinical features of previous GFM1-deficient patients and note seizures in 5/12 patients. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.411 | GFM1 | Rebecca Foulger commented on gene: GFM1: PMID:21119709. In a girl, born of consanguineous parents, with combined oxidative phosphorylation deficiency, Smits et al. (2011) identified a homozygous R250W variant in GFM1. The patient had refractory seizures amongst her phenotypes. This paper is referred to in the review by Tracy Lester. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.411 | GCH1 | Rebecca Foulger Publications for gene: GCH1 were set to 7869202; 17407085; 12552057; 7730309; 31202265 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.410 | GCH1 | Rebecca Foulger Publications for gene: GCH1 were set to 7869202; 17407085; 12552057; 7730309 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.409 | GCH1 | Rebecca Foulger commented on gene: GCH1: Additional evidence for seizures being part of the metabolic disorder comes from PMID:31202265 (Dayasiri et al, 2019) who report a S. Asian child with AR GTPCH (GCH1) deficiency, diagnosed from metabolic testing and family consanguinity. Features included recurrent seizures since 3 months old. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.409 | GCH1 | Rebecca Foulger Publications for gene: GCH1 were set to 7869202; 17407085; 12552057 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.54 | COL3A1 | Ivone Leong Added comment: Comment on mode of inheritance: MOI changed from Monoallelic to Both monoallelic and biallelic based on expert reviews provided. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.54 | COL3A1 | Ivone Leong Mode of inheritance for gene: COL3A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.351 | SIK3 | Rebecca Foulger Phenotypes for gene: SIK3 were changed from ?Spondyloepimetaphyseal dysplasia, Krakow type, 618162 to Spondyloepimetaphyseal dysplasia, Krakow type, 618162 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.350 | SIK3 | Rebecca Foulger Classified gene: SIK3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.350 | SIK3 | Rebecca Foulger Added comment: Comment on list classification: Added SIK3 to panel as a Green gene following communication with Rhiannon Mellis. A mouse model (PMID:22318228) provides additional support: mice show skeletal anomalies (plus dwarfism postnatally). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.350 | SIK3 | Rebecca Foulger Gene: sik3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.349 | SIK3 |
Rebecca Foulger gene: SIK3 was added gene: SIK3 was added to Fetal anomalies. Sources: Other Mode of inheritance for gene: SIK3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SIK3 were set to 30232230; 22318228 Phenotypes for gene: SIK3 were set to ?Spondyloepimetaphyseal dysplasia, Krakow type, 618162 Added comment: Added to panel as suggested by Rhinannon Mellis. One pair of siblings with spondyloepimetaphyseal dysplasia reported in PMID:30232230 (Csukasi et al., 2018) plus one clinical case of suspected skeletal dysplasia prenatally. Sources: Other |
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| Paroxysmal central nervous system disorders v1.0 | Rebecca Foulger promoted panel to version 1.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paroxysmal central nervous system disorders v0.174 | Rebecca Foulger Panel types changed to GMS Rare Disease; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paroxysmal central nervous system disorders v0.173 | CACNB4 | Rebecca Foulger changed review comment from: Reviews by Andrea Nemeth and Jonathan William were uploaded (September 29th 2019) on their behalf based on email discussion of these genes to reach a consensus on the rating. Comments were received over email, and I uploaded an Amber review based on their comments.; to: Reviews by Andrea Nemeth and Jonathan Williams were uploaded (September 29th 2019) on their behalf based on email discussion of these genes to reach a consensus on the rating. Comments were received over email, and I uploaded an Amber review based on their comments. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paroxysmal central nervous system disorders v0.173 | CACNB4 | Rebecca Foulger changed review comment from: Comment on list classification: Downgraded CACNB4 rating from Green to Amber based on GLH review. The most recent comments from Andrea Nemeth and Jonathan William agree that there is only weak evidence to support a gene:disease association. The current evidence comes from PMID:10762541 which reports 1 family (plus another family with epilepsy), and a mouse model.; to: Comment on list classification: Downgraded CACNB4 rating from Green to Amber based on GLH review. The most recent comments from Andrea Nemeth and Jonathan Williams agree that there is only weak evidence to support a gene:disease association. The current evidence comes from PMID:10762541 which reports 1 family (plus another family with epilepsy), and a mouse model. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.230 | KMT2D | Eleanor Williams Classified gene: KMT2D as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.230 | KMT2D | Eleanor Williams Added comment: Comment on list classification: Promoting from red to green as >3 cases reported and phenotype is relevant. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.230 | KMT2D | Eleanor Williams Gene: kmt2d has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.229 | KMT2D | Eleanor Williams Mode of inheritance for gene: KMT2D was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.228 | KMT2D |
Eleanor Williams commented on gene: KMT2D: Associated with Kabuki syndrome 1 #147920 (AD) in OMIM. Short stature and some skeletal features (spine, hips) listed as clinical features. > 3 cases reported in OMIM. |
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| Skeletal dysplasia v1.228 | KMT2D |
Eleanor Williams commented on gene: KMT2D: Associated with Kabuki syndrome 1 #147920 (AD) in OMIM. Short stature and some skeletal features (spine, hips) listed as clinical features. > 3 cases reported in OMIM. |
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| Skeletal dysplasia v1.228 | KAT6B | Eleanor Williams Classified gene: KAT6B as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.228 | KAT6B | Eleanor Williams Added comment: Comment on list classification: More than 3 cases reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.228 | KAT6B | Eleanor Williams Gene: kat6b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.227 | KAT6B | Eleanor Williams Mode of inheritance for gene: KAT6B was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.226 | KAT6B | Eleanor Williams commented on gene: KAT6B: Associated with Genitopatellar syndrome #606170 (AD) in OMIM. Abnormalities of the pelvis, limbs, hands and feet listed. >3 cases reported in OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.226 | KAT6A |
Eleanor Williams commented on gene: KAT6A: Associated with Mental retardation, autosomal dominant 32 #616268 (AD) in OMIM. PMID: 25728777 -Tham et al 2015 - report six individuals from five unrelated families, with mutations in KAT6A detected by whole-exome sequencing. 5 different de novo heterozygous truncating mutations were identified. An additional subject with a 0.23 MB microdeletion including the entire KAT6A reading frame was identified with genome-wide array comparative genomic hybridization. Craniosynostosis was reported in 2 families. No other major skeletal abnormalities were reported. |
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| Skeletal dysplasia v1.226 | IGF1R | Eleanor Williams commented on gene: IGF1R: Associated with Insulin-like growth factor I, resistance to #270450 (AD, AR). More than 3 cases with variants in IFG1R reported in OMIM. Clinical features include short stature due to lack of response to IGF. Clinodactyly and short hands and feet also listed. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.226 | IFIH1 | Eleanor Williams Classified gene: IFIH1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.226 | IFIH1 | Eleanor Williams Added comment: Comment on list classification: 4 cases reported. All have the same gain of function variant. Genomics England clinicians confirm the phenotype is relevant. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.226 | IFIH1 | Eleanor Williams Gene: ifih1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.225 | IFIH1 | Eleanor Williams Phenotypes for gene: IFIH1 were changed from Singleton-Merten syndrome 1 (182250) to Singleton-Merten syndrome 1, 182250 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.224 | IFIH1 | Eleanor Williams Publications for gene: IFIH1 were set to 25620204 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.223 | IFIH1 | Eleanor Williams Added comment: Comment on mode of pathogenicity: A single variant, thought to act as a gain of function, has been identified. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.223 | IFIH1 | Eleanor Williams Mode of pathogenicity for gene: IFIH1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.222 | IFIH1 | Eleanor Williams Mode of inheritance for gene: IFIH1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.221 | IFIH1 |
Eleanor Williams changed review comment from: Associated with Singleton-Merten syndrome 1 #182250 (AD) in OMIM with short stature and various skeletal abnormalities listed as clinical features. PMID: 25620204 - Rutsch et al 2015 - identified the same missense mutation, c.2465G>A (p.Arg822Gln), in IFIH1 in Singleton-Merten syndrome (SMS) patients from two families and a simplex case. Functional studies suggest this is a a gain-of-function IFIH1 mutation. Patients showed early and extreme aortic and valvular calcification, dental anomalies, osteopenia, and acroosteolysis .; to: Associated with Singleton-Merten syndrome 1 #182250 (AD) in OMIM with short stature and various skeletal abnormalities listed as clinical features. PMID: 25620204 - Rutsch et al 2015 - identified the same missense mutation, c.2465G>A (p.Arg822Gln), in IFIH1 in Singleton-Merten syndrome (SMS) patients from two families and a simplex case. Functional studies suggest this is a a gain-of-function IFIH1 mutation. Patients showed early and extreme aortic and valvular calcification, dental anomalies, osteopenia, and acroosteolysis . PMID: 28319323 - Pettersson et al 2018 - identified the same mutation c.2465G>A p.(Arg822Gln), in IFIH1in a mother and daughter with Singleton-Merten syndrome. Patient 1 presented with congenital glaucoma, spastic paraplegia, severe dental anomalies, kyphosis, osteoporosis, recurrent infections, muscle weakness, aortic insufficiency, pericarditis, short stature, and SLE. Her mother presented with milder dental anomalies and finger deformities. |
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| Skeletal dysplasia v1.221 | IFIH1 |
Eleanor Williams commented on gene: IFIH1: Associated with Singleton-Merten syndrome 1 #182250 (AD) in OMIM with short stature and various skeletal abnormalities listed as clinical features. PMID: 25620204 - Rutsch et al 2015 - identified the same missense mutation, c.2465G>A (p.Arg822Gln), in IFIH1 in Singleton-Merten syndrome (SMS) patients from two families and a simplex case. Functional studies suggest this is a a gain-of-function IFIH1 mutation. Patients showed early and extreme aortic and valvular calcification, dental anomalies, osteopenia, and acroosteolysis . |
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| Skeletal dysplasia v1.221 | IDH2 |
Eleanor Williams changed review comment from: Associated with D-2-hydroxyglutaric aciduria 2 #613657 in OMIM. No inheritance pattern given. Clinical features do not list skeletal characteristics. PMID: 20847235 - Kranendijk et al. (2010) - 15 of 17 cases of D-2-hydroxyglutaric aciduria without mutation in the D2HGDH gene a heterozygous mutation was found in the IDH2 gene. 14 had an arg140-to-gln mutation (R140Q) and 1 had an arg140-to-gly mutation (R140G). PMID: 24049096 - Nota et al. (2013) reported a patient with D-2-hydroxyglutaric aciduria-2 in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo. PMID: 22057234 - Pansuriya etal 2011 - state that 'Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). They report somatic heterozygous mutations IDH2 (c.516G>C encoding R172S) in enchondromas (benign cartilage tumors) and in spindle cell hemangiomas (benign vascular lesions). Conclusion - associated with D-2-hydroxyglutaric aciduria but this does not have a skeletal phenotype. Also associated with somatic mutations which can result in Ollier disease and Maffucci syndrome; to: Associated with D-2-hydroxyglutaric aciduria 2 #613657 in OMIM. No inheritance pattern given. Clinical features do not list skeletal characteristics. PMID: 20847235 - Kranendijk et al. (2010) - 15 of 17 cases of D-2-hydroxyglutaric aciduria without mutation in the D2HGDH gene a heterozygous mutation was found in the IDH2 gene. 14 had an arg140-to-gln mutation (R140Q) and 1 had an arg140-to-gly mutation (R140G). Phenotypes of the patients are not given. PMID: 24049096 - Nota et al. (2013) reported two patients with D-2-hydroxyglutaric aciduria-2, one in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo. In the other the mother also had mosacism for R140Q variant. No skeletal phenotypes are reported. PMID: 22057234 - Pansuriya etal 2011 - state that 'Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). They report somatic heterozygous mutations IDH2 (c.516G>C encoding R172S) in enchondromas (benign cartilage tumors) and in spindle cell hemangiomas (benign vascular lesions). Conclusion - associated with D-2-hydroxyglutaric aciduria but this does not have a skeletal phenotype. Also associated with somatic mutations which can result in Ollier disease and Maffucci syndrome |
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| Skeletal dysplasia v1.221 | IDH2 |
Eleanor Williams changed review comment from: PMID: 20847235 - Kranendijk et al. (2010) - 15 of 17 cases of D-2-hydroxyglutaric aciduria without mutation in the D2HGDH gene a heterozygous mutation was found in the IDH2 gene. 14 had an arg140-to-gln mutation (R140Q) and 1 had an arg140-to-gly mutation (R140G). PMID: 24049096 - Nota et al. (2013) reported a patient with D-2-hydroxyglutaric aciduria-2 in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo.; to: Associated with D-2-hydroxyglutaric aciduria 2 #613657 in OMIM. No inheritance pattern given. Clinical features do not list skeletal characteristics. PMID: 20847235 - Kranendijk et al. (2010) - 15 of 17 cases of D-2-hydroxyglutaric aciduria without mutation in the D2HGDH gene a heterozygous mutation was found in the IDH2 gene. 14 had an arg140-to-gln mutation (R140Q) and 1 had an arg140-to-gly mutation (R140G). PMID: 24049096 - Nota et al. (2013) reported a patient with D-2-hydroxyglutaric aciduria-2 in whom mosaicism for the R140Q mutation in IDH2 had occurred de novo. PMID: 22057234 - Pansuriya etal 2011 - state that 'Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). They report somatic heterozygous mutations IDH2 (c.516G>C encoding R172S) in enchondromas (benign cartilage tumors) and in spindle cell hemangiomas (benign vascular lesions). Conclusion - associated with D-2-hydroxyglutaric aciduria but this does not have a skeletal phenotype. Also associated with somatic mutations which can result in Ollier disease and Maffucci syndrome |
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| Skeletal dysplasia v1.221 | EP300 |
Eleanor Williams commented on gene: EP300: Associated with Rubinstein-Taybi syndrome 2 #613684 (AD) in OMIM with Broad thumbs, Square distal fingertips, Syndactyly (in some patients) and Broad great toes listed as skeletal clinical features. Heterozygous mutations reported in > 3 cases in OMIM. |
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| Skeletal dysplasia v1.221 | COG1 | Eleanor Williams Classified gene: COG1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.221 | COG1 | Eleanor Williams Added comment: Comment on list classification: 3 unrelated cases with plausible disease causing variants in the gene reported and a relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.221 | COG1 | Eleanor Williams Gene: cog1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.220 | COG1 |
Eleanor Williams changed review comment from: Associated with Congenital disorder of glycosylation, type IIg #611209 (AR) in OMIM.; to: Associated with Congenital disorder of glycosylation, type IIg #611209 (AR) in OMIM. Clinical features include short stature, several skeletal features such as scoliosis and vertebral abnormalities. PMID: 16537452 - Foulquier et al 2006 - describe a patient with a mild form of congenital disorder of glycosylation type II with a homozygous insertion of a single nucleotide (2659-2660insC), which is predicted to lead to a premature translation stop and truncation of the C terminus of the Cog1 protein by 80 amino acids. Both parents were shown to be heterozygous for this mutation. Her skeletal features included small hands and feet, rhizomelic short stature. PMID: 19008299 - Zeevaert et al 2009 - two patients (one with consanguineous Greek-Turkish parents, the other with unrelated Bulgarian parents) with a cerebrocostomandibular-like syndrome and an intronic mutation, c.1070+5G>A, that disrupts a splice donor site and leads to skipping of exon 6, a frameshift and a premature stopcodon in exon 7. Patient 1's characteristics included multiple congenital abnormalities including Pierre-Robin sequence (cleft palate, micrognathia and glossoptosis), costovertebral anomalies including osteopenia, ribfusions and posterior rib gaps, butterfly vertebrae, misalignment of the vertebrae and a clubfoot on the right. Patient 2 presented with rhizomelic shortening of upper limbs, ulnar deviation of fingers, thoracic scoliosis, hypospadias-I and left-side cryptorchidism among other features. 3 unrelated cases. |
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| Skeletal dysplasia v1.220 | COG1 | Eleanor Williams commented on gene: COG1: Associated with Congenital disorder of glycosylation, type IIg #611209 (AR) in OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Additional findings health related v0.90 | RET | Ellen McDonagh Transcript for gene RET was changed from ENST00000355710.7 to ENST00000355710.8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Additional findings health related v0.89 | MSH6 |
Ellen McDonagh Source Additional Findings was removed from MSH6. Source ACMG was removed from MSH6. Source Other was added to MSH6. Phenotypes for gene: MSH6 were changed from ENST00000234420.9; Bowel cancer predisposition; Hereditary non-polyposis colorectal cancer; Adult only to Bowel cancer predisposition; Hereditary non-polyposis colorectal cancer; Adult only Transcript for gene MSH6 was changed from None to ENST00000234420.9 |
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| Additional findings health related v0.88 | MUTYH |
Ellen McDonagh Source Additional Findings was removed from MUTYH. Source ACMG was removed from MUTYH. Source Other was added to MUTYH. Phenotypes for gene: MUTYH were changed from ENST00000450313.5; Bowel cancer predisposition; MYH-associated polyposis; Adult only to Bowel cancer predisposition; MYH-associated polyposis; Adult only Transcript for gene MUTYH was changed from None to ENST00000450313.5 |
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| Additional findings health related v0.87 | PCSK9 |
Ellen McDonagh Source Additional Findings was removed from PCSK9. Source ACMG was removed from PCSK9. Source Other was added to PCSK9. Phenotypes for gene: PCSK9 were changed from ENST00000302118.5; Familial hypercholesterolaemia; Adult and child to Familial hypercholesterolaemia; Adult and child Transcript for gene PCSK9 was changed from None to ENST00000302118.5 |
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| Additional findings health related v0.86 | RET |
Ellen McDonagh Phenotypes for gene: RET were changed from ENST00000355710.7; Other cancer predisposition; Myltiple endocrine Neoplasia Type 2; Adult and child to Other cancer predisposition; Myltiple endocrine Neoplasia Type 2; Adult and child Transcript for gene RET was changed from None to ENST00000355710.7 |
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| Additional findings health related v0.85 | VHL |
Ellen McDonagh Source Additional Findings was removed from VHL. Source ACMG was removed from VHL. Source Other was added to VHL. Phenotypes for gene: VHL were changed from ENST00000256474.2; Other cancer predisposition; Von Hippel Lindau Syndrome; Adult and child to Other cancer predisposition; Von Hippel Lindau Syndrome; Adult and child Transcript for gene VHL was changed from None to ENST00000256474.2 |
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| Skeletal dysplasia v1.220 | SULF1 |
Eleanor Williams Tag deletions tag was added to gene: SULF1. Tag currently-ngs-unreportable tag was added to gene: SULF1. |
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| Skeletal dysplasia v1.220 | SLCO5A1 |
Eleanor Williams Tag deletions tag was added to gene: SLCO5A1. Tag currently-ngs-unreportable tag was added to gene: SLCO5A1. |
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| Familial hypercholesterolaemia (GMS) v1.0 | Ellen McDonagh promoted panel to version 1.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial hypercholesterolaemia (GMS) v0.7 | Ellen McDonagh Panel types changed to GMS Rare Disease; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Familial hypercholesterolaemia (GMS) v0.6 | Ellen McDonagh List of related panels changed from to R134 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.220 | OAT |
Eleanor Williams changed review comment from: Associated with Gyrate atrophy of choroid and retina with or without ornithinemia #258870 (AR) in OMIM but no skeletal phenotypes listed in clinical features. This gene is not listed in Bonafe et al 2015 (Nosology and Classification of Genetic Skeletal Disorders: 2015 Revision) PMID: 26394607 or Mortier et al 2019 (Nosology and classification of genetic skeletal disorders: 2019 revision). PMID: 31633310; to: Associated with Gyrate atrophy of choroid and retina with or without ornithinemia #258870 (AR) in OMIM but no skeletal phenotypes listed in clinical features. This gene is not listed in Bonafe et al 2015 (Nosology and Classification of Genetic Skeletal Disorders: 2015 Revision) PMID: 26394607 or Mortier et al 2019 (Nosology and classification of genetic skeletal disorders: 2019 revision). PMID: 31633310 A PubMed search did not find any relevant publications. |
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| Skeletal dysplasia v1.220 | SULF1 |
Eleanor Williams commented on gene: SULF1: Not associated with any phenotype in OMIM or Gene2Phenotype. PMID: 20602915 - Isidor et al 2010 - using whole-genome oligonucleotide array CGH, they identified an interstitial deletion at 8q13 in 5 patients from 4 unrelated families with Mesomelia-synostoses syndrome. The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1 and SLCO5A1. Breakpoint sequence analyses performed in two families showed nonrecurrent deletions. Codeletion of SULF1 and SLCO5A1was found in all patients, suggesting that haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS. PMID: 28328141 - Kohmoto et al 2017 - report the first Japanese case with MSS diagnosed by detecting an 8q13 deletion (581 Kb monoallelic deletion) that resulted from a unique, distant L1s‐mediated unequal NAHR event, which is different from the possible mechanisms proposed in previously reported cases. The deletion encompasses SULF1, SLCO5A1, and LINC01603. The size of the 8q13 deletion was different from those of any of the four reported deletions responsible for MSS (Isidor et al., 2010). The deletion could not be confirmed as de novo because of the unavailability of parental DNA. PMID: 30450550 - Dardis et al 2019 - describe the first patient affected by MSS without the previously described 8q13 deletions. Patient is an 8‐year‐old 46,XY male presenting the radiological and clinical hallmarks of MSS. Microdeletions of SULF1 and SLCO5A1 genes at 8q13 were absent. Sequencing of SULF1 and SLCO5A1 found 4 polymorphisms but no pathogenic mutations. However, it was found that there was monoallelic expression of SULF1 in the patient's cells, likely leading to SULF1 haploinsufficiency. There may be either a deletion of a portion of SULF1 gene not detectable by PCR or CGH array or mutations or epigenetic alterations in sequences that contribute to the regulation of SULF1 expression. Summary, there are 5 cases where deletions covering both SULF1 and SLCO5A1 are found in patients with MSS. There is one case of MSS in a patient with no detectable deletions of SULF1 and SLCO5A1, but with monoallelic expression of SULF1. There is no current regions curated by ClinGen that cover these genes. |
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| Skeletal dysplasia v1.220 | SLCO5A1 |
Eleanor Williams commented on gene: SLCO5A1: Not associated with any phenotype in OMIM or Gene2Phenotype. PMID: 20602915 - Isidor et al 2010 - using whole-genome oligonucleotide array CGH, they identified an interstitial deletion at 8q13 in 5 patients from 4 unrelated families with Mesomelia-synostoses syndrome. The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1 and SLCO5A1. Breakpoint sequence analyses performed in two families showed nonrecurrent deletions. Codeletion of SULF1 and SLCO5A1was found in all patients, suggesting that haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS. PMID: 28328141 - Kohmoto et al 2017 - report the first Japanese case with MSS diagnosed by detecting an 8q13 deletion (581 Kb monoallelic deletion) that resulted from a unique, distant L1s‐mediated unequal NAHR event, which is different from the possible mechanisms proposed in previously reported cases. The deletion encompasses SULF1, SLCO5A1, and LINC01603. The size of the 8q13 deletion was different from those of any of the four reported deletions responsible for MSS (Isidor et al., 2010). The deletion could not be confirmed as de novo because of the unavailability of parental DNA. PMID: 30450550 - Dardis et al 2019 - describe the first patient affected by MSS without the previously described 8q13 deletions. Patient is an 8‐year‐old 46,XY male presenting the radiological and clinical hallmarks of MSS. Microdeletions of SULF1 and SLCO5A1 genes at 8q13 were absent. Sequencing of SULF1 and SLCO5A1 found 4 polymorphisms but no pathogenic mutations. However, it was found that there was monoallelic expression of SULF1 in the patient's cells, likely leading to SULF1 haploinsufficiency. There may be either a deletion of a portion of SULF1 gene not detectable by PCR or CGH array or mutations or epigenetic alterations in sequences that contribute to the regulation of SULF1 expression. Summary, there are 5 cases where deletions covering both SULF1 and SLCO5A1 are found in patients with MSS. There is one case of MSS in a patient with no detectable deletions of SULF1 and SLCO5A1, but with monoallelic expression of SULF1. There is no current regions curated by ClinGen that cover these genes. |
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| Rare genetic inflammatory skin disorders v0.15 | CARD9 | Catherine Snow Mode of inheritance for gene: CARD9 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.220 | RAD21 |
Eleanor Williams changed review comment from: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. Clinical features listed include short stature and limb defects. OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short (1 patients) and thin (1 patient) fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified. Other publications with patients with Cornelia de Lange and RAD21 variants PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay. PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance. PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance PMID: 27620904 - Martinez et al., 2017 - 1 patient; to: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. Clinical features listed include short stature and limb defects. OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short (1 patients) and thin (1 patient) fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified. Other publications with patients with Cornelia de Lange and RAD21 variants: PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay. PMID: 24378232 - Minor et al., 2014 - 2 patients with atypic Cornelia de Lange. Patient 1 - in frame deletion of exon 13 - presented with developmental delay, hypospadias, inguinal hernia and dysmorphic features, mild 5th finger clinodactyly. This deletion was found to be inherited from the mother who had a history of melanoma and other unspecified medical problems. Patient 2 - c.592_593dup frameshift mutation - presented with developmental delay, characteristic facial features, hirsutism, and hand and feet anomalies (clinodactyly, syndactyly). The mother had the same frameshift mutation showing incomplete penetrance. PMID: 27882533 - Boyle et al., 2017 - patient with microcephaly and classical CdLS facial features with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance. PMID: 27620904 - Martinez et al., 2017 - 92 patients recruited with syndromic intellectual disability. 1 patient identified with a variant in RAD21. A diagnosis of CdLS was made. |
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| Hypertrophic cardiomyopathy v1.78 | MYBPC3 | Ivone Leong Added comment: Comment on mode of inheritance: MOI changed due to evidence in OMIM that there are patients who are biallelic for variants in this gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypertrophic cardiomyopathy v1.78 | MYBPC3 | Ivone Leong Mode of inheritance for gene: MYBPC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.220 | RAD21 | Eleanor Williams Classified gene: RAD21 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.220 | RAD21 | Eleanor Williams Added comment: Comment on list classification: Promoted from red to amber. 2 cases reported in OMIM with SNV and short stature (1 case) and limb defects (2 cases). Other cases of deletions covering this gene and a similar phenotype are also reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.220 | RAD21 | Eleanor Williams Gene: rad21 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.219 | RAD21 |
Eleanor Williams changed review comment from: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short (1 patients) and thin (1 patient) fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified. Other publications with patients with Cornelia de Lange and RAD21 variants PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay. PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance. PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance PMID: 27620904 - Martinez et al., 2017 - 1 patient; to: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. Clinical features listed include short stature and limb defects. OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short (1 patients) and thin (1 patient) fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified. Other publications with patients with Cornelia de Lange and RAD21 variants PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay. PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance. PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance PMID: 27620904 - Martinez et al., 2017 - 1 patient |
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| Skeletal dysplasia v1.219 | RAD21 |
Eleanor Williams changed review comment from: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short and thin fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified. Other publications with patients with Cornelia de Lange and RAD21 variants PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay. PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance. PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance PMID: 27620904 - Martinez et al., 2017 - 1 patient; to: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short (1 patients) and thin (1 patient) fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified. Other publications with patients with Cornelia de Lange and RAD21 variants PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay. PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance. PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance PMID: 27620904 - Martinez et al., 2017 - 1 patient |
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| Skeletal dysplasia v1.219 | RAD21 |
Eleanor Williams changed review comment from: OMIM: - 2 cases reported in OMIM (PMID: 22633399, Deardorff et al 2012) plus 3 patients with overlapping deletions covering RAD21 (aswell as other genes). Other publications with patients with Cornelia de Lange and RAD21 variants PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance. PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance PMID: 27620904 - Martinez et al., 2017 - 1 patient; to: Associated with Cornelia de Lange syndrome 4 614701 in OMIM. OMIM: - 2 cases reported in OMIM with Cornelia de Lange syndrome-4 (PMID: 22633399, Deardorff et al 2012) with de novo heterozygous missense mutations in RAD21. Phenotypic features include Clinodactyly, short and thin fingers and additional skeletal features of pectus carinatum, coxa vara, short femoral neck in one case. An additional 3 patients with overlapping deletions covering RAD21 (aswell as other genes) were identified. Other publications with patients with Cornelia de Lange and RAD21 variants PMID: 30716475 - Dorval et al 2019 - 1 patient - mild phenotype - gastro-oesophageal reflux, progressive microcephaly, which stabilised at about – 3SD, moderate fine motor delay and speech delay. PMID: 24378232 - Minor et al., 2014 - 2 patients. In one case the mother had the same frameshift mutation showing incomplete penetrance. PMID: 27882533 - Boyle et al., 2017 - patient with a single bp deletion (c.704delG) in RAD21 predicted to result in a premature stop codon [p.(Ser235Ilefs*19)]. The deletion was found in the mother and the two aunts of the index patient, and none of them had been suspected of having CdLS or a cohesinopathy prior to this study - suggests incomplete penetrance PMID: 27620904 - Martinez et al., 2017 - 1 patient |
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| Skeletal dysplasia v1.219 | OAT |
Eleanor Williams commented on gene: OAT: Associated with Gyrate atrophy of choroid and retina with or without ornithinemia #258870 (AR) in OMIM but no skeletal phenotypes listed in clinical features. This gene is not listed in Bonafe et al 2015 (Nosology and Classification of Genetic Skeletal Disorders: 2015 Revision) PMID: 26394607 or Mortier et al 2019 (Nosology and classification of genetic skeletal disorders: 2019 revision). PMID: 31633310 |
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| Skeletal dysplasia v1.219 | CKAP2L |
Eleanor Williams commented on gene: CKAP2L: Associated with Filippi syndrome #272440 (AR) in OMIM. Mainly a digital phenotype. PMID: 25439729 - Hussain et al 2014 - performed homozygosity mapping and whole-exome sequencing in a Sardinian family with two children with Filippi syndrome and identified a homozygous frameshift mutation, c.571dupA (p.Ile191Asnfs∗6), in CKAP2L which segregated with the disease in the family. They then sequenced CKAP2L in eight additional Filippi-syndrome-affected families (one from Italy, one from Poland, one from Turkey, and five from the UK) and identified five additional mutations in four of the further eight families affected by Filippi syndrome. Sufficient cases reported, but need to assess whether the phenotype is appropriate for the skeletal dysplasia panel. It is green on the Limb disorders panel. |
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| Skeletal dysplasia v1.219 | ARID1B |
Eleanor Williams commented on gene: ARID1B: Associated with Coffin-Siris syndrome 1 #135900 (AD) in OMIM. Clinical features list short stature in some patients, but mainly a limb phenotype including hypoplastic digits and nails. OMIM lists many cases of variants in ARID1B reported in patients with Coffin-Siris syndrome. |
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| Skeletal dysplasia v1.219 | AKT1 |
Eleanor Williams changed review comment from: Associated with several phenotypes in OMIM including Proteus syndrome, somatic # 176920. Proteus syndrome features overgrowth of body parts and is associated with mosaicism for a somatic activating mutation in the AKT1 gene. The Genomics England clinical team do not consider this appropriate for a green rating on the skeletal dysplasia panel.; to: Associated with several phenotypes in OMIM including Proteus syndrome, somatic # 176920. Proteus syndrome features overgrowth of body parts and is associated with mosaicism for a somatic activating mutation in the AKT1 gene. PMID: 21793738 - Lindhurst et al 2011 - Of 29 patients with the Proteus syndrome, 26 had a somatic activating mutation (c.49G→A, p.Glu17Lys) in the oncogene AKT1. Tissues and cell lines from patients with the Proteus syndrome harbored admixtures of mutant alleles that ranged from 1% to approximately 50%. Mutant cell lines showed greater AKT phosphorylation than did control cell lines. The Genomics England clinical team do not consider this appropriate for a green rating on the skeletal dysplasia panel. |
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| Skeletal dysplasia v1.219 | AKT1 |
Eleanor Williams commented on gene: AKT1: Associated with several phenotypes in OMIM including Proteus syndrome, somatic # 176920. Proteus syndrome features overgrowth of body parts and is associated with mosaicism for a somatic activating mutation in the AKT1 gene. The Genomics England clinical team do not consider this appropriate for a green rating on the skeletal dysplasia panel. |
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| Skeletal dysplasia v1.219 | TWIST2 | Eleanor Williams Classified gene: TWIST2 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.219 | TWIST2 | Eleanor Williams Added comment: Comment on list classification: Removing this gene from the panel as the OMIM phenotypes to not have a clear skeletal phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.219 | TWIST2 | Eleanor Williams Gene: twist2 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.63 | THPO | Eleanor Williams Classified gene: THPO as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.63 | THPO | Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber. Two cases of Thrombocythemia with limb defects and variants in THPO reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.63 | THPO | Eleanor Williams Gene: thpo has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v1.62 | THPO |
Eleanor Williams gene: THPO was added gene: THPO was added to Limb disorders. Sources: Literature Mode of inheritance for gene: THPO was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: THPO were set to 19553636; 22453305 Phenotypes for gene: THPO were set to Thrombocythemia 1, 187950 Review for gene: THPO was set to AMBER Added comment: Associated with Thrombocythemia 1 #187950 (AD) in OMIM. PMID: 19553636 - Graziano et al 2009 - report where the father has thrombocythemia and limb defects (absence of forearm and hand, absence of foot). Two sons had milder lower limb defects. A G185T heterozygous mutation was detected in THPO. The grandfather was found to have the variant and had thrombocythemia but no limb defect. PMID: 22453305 - Stockklausner et al 2012 - report two families with Hereditary thrombocythemia resulting from a THPO c.13+1 G>C mutation in the splice donor of intron 3. In one family there were coexisting distal limb defects in 2 out of 4 individuals with thrombocythemia (complex limb defects of the left hand in one individual, and absent proximal, middle, and distal phalanges at digits 3–5, a dysplastic proximal phalanx at digit 2 with absent middle and distal phalanx and shortened metacarpal bones at digits 3 and 4, carpal bones were partly fused to metacarpal bones at digits 2–5 in the other). Two cases reported with a limb defect and no clear wider skeletal phenotype. Sources: Literature |
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| Skeletal dysplasia v1.218 | THPO | Eleanor Williams Classified gene: THPO as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.218 | THPO | Eleanor Williams Added comment: Comment on list classification: Demoted from Green to red. Only two cases reported with a limb defect and no clear wider skeletal phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.218 | THPO | Eleanor Williams Gene: thpo has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.217 | THPO |
Eleanor Williams commented on gene: THPO: Associated with Thrombocythemia 1 #187950 (AD) in OMIM. PMID: 19553636 - Graziano et al 2009 - report where the father has thrombocythemia and limb defects (absence of forearm and hand, absence of foot). Two sons had milder lower limb defects. A G185T heterozygous mutation was detected in THPO. The grandfather was found to have the variant and had thrombocythemia but no limb defect. PMID: 22453305 - Stockklausner et al 2012 - report two families with Hereditary thrombocythemia resulting from a THPO c.13+1 G>C mutation in the splice donor of intron 3. In one family there were coexisting distal limb defects in 2 out of 4 individuals with thrombocythemia (complex limb defects of the left hand in one individual, and absent proximal, middle, and distal phalanges at digits 3–5, a dysplastic proximal phalanx at digit 2 with absent middle and distal phalanx and shortened metacarpal bones at digits 3 and 4, carpal bones were partly fused to metacarpal bones at digits 2–5 in the other). |
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| Skeletal dysplasia v1.217 | ASXL1 |
Eleanor Williams changed review comment from: Associated with Bohring-Opitz syndrome #605039 (AD) in OMIM. Clinical features listed include short stature and a number of skeletal features including upper limb rhizomelia.; to: Associated with Bohring-Opitz syndrome #605039 (AD) in OMIM. Clinical features listed include short stature and a number of skeletal features including upper limb rhizomelia. Genomics England clinical team feel that there are sufficient relevant phenotypes to leave green. |
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| Skeletal dysplasia v1.217 | ASXL1 | Eleanor Williams commented on gene: ASXL1: Associated with Bohring-Opitz syndrome #605039 (AD) in OMIM. Clinical features listed include short stature and a number of skeletal features including upper limb rhizomelia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.217 | TGDS |
Eleanor Williams commented on gene: TGDS: Associated with Catel-Manzke syndrome #616145 (AR) in OMIM. PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction they showed that the mutation c.298G>T is probably a founder mutation In 7 patients with Catel-Manzke syndrome (616145), Ehmke et al. (2014) identified homozygosity or compound heterozygosity for mutations in the TGDS gene |
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| Skeletal dysplasia v1.217 | WRN | Eleanor Williams Mode of inheritance for gene: WRN was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.217 | WRN | Eleanor Williams Mode of inheritance for gene: WRN was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.216 | WRN |
Eleanor Williams commented on gene: WRN: Associated with Werner syndrome #277700 (AR) in OMIM with Osteoporosis and slender limbs listed as clinical features. From Genetics Home Reference "Werner syndrome is characterized by the dramatic, rapid appearance of features associated with normal aging. Individuals with this disorder typically grow and develop normally until they reach puberty. Affected teenagers usually do not have a growth spurt, resulting in short stature". Numerous variants reported in the RECQL2/WRN gene in association with Werner syndrome in OMIM. |
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| Arrhythmogenic right ventricular cardiomyopathy v1.43 | FLNC | Ellen McDonagh Classified gene: FLNC as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arrhythmogenic right ventricular cardiomyopathy v1.43 | FLNC | Ellen McDonagh Added comment: Comment on list classification: Promoted from Amber to Green based on two expert reviews and Definitive gene validity curation by ClinGen Expert Panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arrhythmogenic right ventricular cardiomyopathy v1.43 | FLNC | Ellen McDonagh Gene: flnc has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Arrhythmogenic right ventricular cardiomyopathy v1.42 | FLNC | Ellen McDonagh Mode of inheritance for gene: FLNC was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy and conduction defects v1.64 | PRDM16 | Ellen McDonagh Classified gene: PRDM16 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy and conduction defects v1.64 | PRDM16 | Ellen McDonagh Added comment: Comment on list classification: Promoted to Amber as not enough evidence at this stage to be Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dilated Cardiomyopathy and conduction defects v1.64 | PRDM16 | Ellen McDonagh Gene: prdm16 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.408 | HCN2 | Rebecca Foulger Added comment: Comment on mode of inheritance: Kept MOI as 'BOTH monoallelic and biallelic' as supported by reviews from Helen Lord and Alison Callaway, and literature (PMID:22131395). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.408 | HCN2 | Rebecca Foulger Mode of inheritance for gene: HCN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1102 | IL3RA | Eleanor Williams Added comment: Comment on mode of inheritance: This gene is in the pseudoautosomal region shared between chromosomes X and Y. The mode of inheritance should therefore be set to Biallelic or Monoallelic once more cases establish the inheritance pattern. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1102 | IL3RA | Eleanor Williams Mode of inheritance for gene: IL3RA was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1101 | DHRSX | Eleanor Williams Added comment: Comment on mode of inheritance: This gene is in the pseudoautosomal region shared between chromosomes X and Y. The mode of inheritance should therefore be set to Biallelic or Monoallelic once more cases establish the inheritance pattern. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1101 | DHRSX | Eleanor Williams Mode of inheritance for gene: DHRSX was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1100 | CRLF2 | Eleanor Williams Added comment: Comment on mode of inheritance: This gene is in the pseudoautosomal region shared between chromosomes X and Y. The mode of inheritance should therefore be set to Biallelic or Monoallelic once more cases establish the inheritance pattern. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1100 | CRLF2 | Eleanor Williams Mode of inheritance for gene: CRLF2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1099 | AKAP17A | Eleanor Williams Added comment: Comment on mode of inheritance: This gene is in the pseudoautosomal region shared between chromosomes X and Y. The mode of inheritance should therefore be set to Biallelic or Monoallelic once more cases establish the inheritance pattern. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1099 | AKAP17A | Eleanor Williams Mode of inheritance for gene: AKAP17A was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Laterality disorders and isomerism v0.51 | CCDC39 | Matthew Edwards reviewed gene: CCDC39: Rating: GREEN; Mode of pathogenicity: None; Publications: 21131972, 23255504; Phenotypes: OMIM 613807 Ciliary dyskinesia, primary, 14; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.53 | TGFB3 | Ivone Leong Publications for gene: TGFB3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.52 | SKI | Ivone Leong Publications for gene: SKI were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.51 | PRKG1 | Ivone Leong Publications for gene: PRKG1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.50 | NOTCH1 | Ivone Leong Publications for gene: NOTCH1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.49 | MYLK | Ivone Leong Publications for gene: MYLK were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.48 | FBN2 | Ivone Leong Publications for gene: FBN2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.47 | EFEMP2 | Ivone Leong Publications for gene: EFEMP2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.46 | COL5A2 | Ivone Leong Publications for gene: COL5A2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.45 | CBS | Ivone Leong Publications for gene: CBS were set to 747076; 18799873; 16733360; 2041851; 23525608 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection v1.109 | COL5A2 | Ivone Leong Publications for gene: COL5A2 were set to 26188975; 29543232 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection v1.108 | COL5A2 | Ivone Leong Publications for gene: COL5A2 were set to 26188975 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection v1.107 | COL5A1 | Ivone Leong Publications for gene: COL5A1 were set to 26188975; 10946364 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection v1.106 | COL3A1 | Ivone Leong Publications for gene: COL3A1 were set to 25758994 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection v1.105 | COL1A2 | Ivone Leong Publications for gene: COL1A2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection v1.104 | BGN | Ivone Leong Publications for gene: BGN were set to 27632686 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v1.0 | Ivone Leong promoted panel to version 1.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.99 | HMX1 | Ivone Leong Added comment: Comment on mode of inheritance: MOI corrected from Both monoallelic and biallelic to Biallelic based on reviewers comments and OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.99 | HMX1 | Ivone Leong Mode of inheritance for gene: HMX1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Additional findings health related v0.84 | MSH2 |
Ellen McDonagh Source Additional Findings was removed from MSH2. Source ACMG was removed from MSH2. Source Expert list was added to MSH2. Phenotypes for gene: MSH2 were changed from ENST00000233146.6; Bowel cancer predisposition; Hereditary non-polyposis colorectal cancer; Adult only to Bowel cancer predisposition; Hereditary non-polyposis colorectal cancer; Adult only Transcript for gene MSH2 was changed from None to ENST00000233146.6 |
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| Additional findings health related v0.83 | MLH1 |
Ellen McDonagh Source Additional Findings was removed from MLH1. Source ACMG was removed from MLH1. Source Expert list was added to MLH1. Phenotypes for gene: MLH1 were changed from ENST00000231790.6; Bowel cancer predisposition; Hereditary non-polyposis colorectal cancer; Adult only to Bowel cancer predisposition; Hereditary non-polyposis colorectal cancer; Adult only Transcript for gene MLH1 was changed from None to ENST00000231790.6 |
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| Additional findings health related v0.82 | MEN1 |
Ellen McDonagh Source Additional Findings was removed from MEN1. Source ACMG was removed from MEN1. Source Expert list was added to MEN1. Phenotypes for gene: MEN1 were changed from ENST00000394374.6; Other cancer predisposition; Myltiple endocrine Neoplasia Type 1; Adult and child to Other cancer predisposition; Myltiple endocrine Neoplasia Type 1; Adult and child Transcript for gene MEN1 was changed from None to ENST00000394374.6 |
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| Additional findings health related v0.81 | LDLR |
Ellen McDonagh Source Additional Findings was removed from LDLR. Source ACMG was removed from LDLR. Source Expert list was added to LDLR. Phenotypes for gene: LDLR were changed from ENST00000558518.5; Familial hypercholesterolaemia; Adult and child to Familial hypercholesterolaemia; Adult and child Transcript for gene LDLR was changed from None to ENST00000558518.5 |
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| Additional findings reproductive carrier status v0.3 | CFTR |
Ellen McDonagh Phenotypes for gene: CFTR were changed from ENST00000003084.10; Carrier status; Cystic Fibrosis; Adult-only to Carrier status; Cystic Fibrosis; Adult-only Transcript for gene CFTR was changed from None to ENST00000003084.10 |
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| Additional findings health related v0.80 | BRCA2 |
Ellen McDonagh Source Additional Findings was removed from BRCA2. Source ACMG was removed from BRCA2. Source Expert list was added to BRCA2. Phenotypes for gene: BRCA2 were changed from ENST00000544455.5; Breast and ovarian cancer predisposition; Adult only to Breast and ovarian cancer predisposition; Adult only Transcript for gene BRCA2 was changed from None to ENST00000544455.5 |
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| Additional findings health related v0.79 | BRCA1 |
Ellen McDonagh Source Additional Findings was removed from BRCA1. Source ACMG was removed from BRCA1. Source Expert list was added to BRCA1. Transcript for gene BRCA1 was changed from None to ENST00000357654.8 |
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| Additional findings health related v0.78 | APOB |
Ellen McDonagh Phenotypes for gene: APOB were changed from ENST00000233242.5; Familial hypercholesterolaemia; Adult and child to Familial hypercholesterolaemia; Adult and child Transcript for gene APOB was changed from None to ENST00000233242.5 |
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| Additional findings health related v0.77 | APC |
Ellen McDonagh Source Additional Findings was removed from APC. Source ACMG was removed from APC. Source Expert list was added to APC. Phenotypes for gene: APC were changed from ENST00000257430.8; Bowel cancer predisposition; Familial Adenomatous Polyposis; Adult and child to Bowel cancer predisposition; Familial Adenomatous Polyposis; Adult and child Transcript for gene APC was changed from None to ENST00000257430.9 |
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| Structural eye disease v0.98 | WDR37 | Ivone Leong Classified gene: WDR37 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.98 | WDR37 | Ivone Leong Added comment: Comment on list classification: New gene submitted by reviewer. I have made this gene a Red gene as the current panel has already been finalised. This gene can be considered for a new gene rating in the next review iteration. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.98 | WDR37 | Ivone Leong Gene: wdr37 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.348 | GLA |
Rebecca Foulger changed review comment from: Added GLA to panel based on Green rating on Fetal hydrops panel V1.16, following email communication from Dominic McMullan (West Midlands, Oxford and Wessex GLH). Sources: Other; to: Added GLA to panel as a Green gene based on Green rating on Fetal hydrops panel V1.16, following email communication from Dominic McMullan (West Midlands, Oxford and Wessex GLH). Sources: Other |
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| Fetal anomalies v0.348 | GLA | Rebecca Foulger Classified gene: GLA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.348 | GLA | Rebecca Foulger Gene: gla has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.347 | GLA |
Rebecca Foulger gene: GLA was added gene: GLA was added to Fetal anomalies. Sources: Other Mode of inheritance for gene: GLA was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: GLA were set to Fabry disease, 301500 Added comment: Added GLA to panel based on Green rating on Fetal hydrops panel V1.16, following email communication from Dominic McMullan (West Midlands, Oxford and Wessex GLH). Sources: Other |
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| Structural eye disease v0.97 | WDR37 | Ivone Leong Publications for gene: WDR37 were set to PMID:31327510, PMID:31327508 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.96 | Ivone Leong Panel types changed to GMS Rare Disease; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v2.1 | Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v2.0 | Ivone Leong promoted panel to version 2.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.228 | RDH12 | Ivone Leong Added comment: Comment on mode of inheritance: MOI has been updated from Biallelic to BOTH monoallelic and biallelic based on PMID: 31505163, which describes both autosomal dominant and recessive retinal phenotypes. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.228 | RDH12 | Ivone Leong Mode of inheritance for gene: RDH12 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.227 | RDH12 | Ivone Leong Publications for gene: RDH12 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.226 | NMNAT1 | Ivone Leong Publications for gene: NMNAT1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.225 | CSPP1 | Ivone Leong Phenotypes for gene: CSPP1 were changed from Genetic Retinal Degeneration Conditions; Joubert syndrome 21 to Genetic Retinal Degeneration Conditions; Joubert syndrome 21,615636 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.224 | COL18A1 | Ivone Leong Phenotypes for gene: COL18A1 were changed from Knobloch Syndrome Type I to Knobloch Syndrome Type I, 267750 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.223 | CNGA3 | Ivone Leong Phenotypes for gene: CNGA3 were changed from Achromatopsia; Achromatopsia-2; Eye Disorders; Achromatopsia, Cone, and Cone-rod Dystrophy to Achromatopsia; Achromatopsia-2, 216900; Eye Disorders; Achromatopsia, Cone, and Cone-rod Dystrophy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.222 | CLRN1 | Ivone Leong Phenotypes for gene: CLRN1 were changed from Eye Disorders; ?Usher syndrome, type 3A, 276902Retinitis pigmentosa 61, 614180; Retinitis Pigmentosa, Dominant; Retinitis pigmentosa to Eye Disorders; ?Usher syndrome, type 3A, 276902; Retinitis pigmentosa 61, 614180 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.221 | CEP290 | Ivone Leong Publications for gene: CEP290 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.220 | CDHR1 | Ivone Leong Phenotypes for gene: CDHR1 were changed from Achromatopsia, Cone, and Cone-rod Dystrophy; Eye Disorders; Cone-Rod Dystrophy, Recessive; Cone-rod dystrophy 15, 613660 to Achromatopsia, Cone, and Cone-rod Dystrophy; Eye Disorders; Cone-Rod Dystrophy, Recessive; Cone-rod dystrophy 15, 613660; Retinitis pigmentosa 65, 613660 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.219 | CC2D2A | Ivone Leong Phenotypes for gene: CC2D2A were changed from COACH syndrome; Joubert syndrome 9; Meckel syndrome 6; Eye Disorders to COACH syndrome, 216360; Joubert syndrome 9, 612285; Meckel syndrome 6, 612284; Eye Disorders | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.218 | BBS9 | Ivone Leong Phenotypes for gene: BBS9 were changed from Eye Disorders to Eye Disorders; Bardet-Biedl syndrome 9, 615986 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.217 | BBS7 | Ivone Leong Phenotypes for gene: BBS7 were changed from Eye Disorders to Eye Disorders; Bardet-Biedl syndrome 7, 615984 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.216 | BBS5 | Ivone Leong Phenotypes for gene: BBS5 were changed from Eye Disorders; Bardet-Biedl syndrome 5 to Eye Disorders; Bardet-Biedl syndrome 5, 615983 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.215 | BBS4 | Ivone Leong Phenotypes for gene: BBS4 were changed from Eye Disorders; Bardet-Biedl syndrome 4 to Eye Disorders; Bardet-Biedl syndrome 4, 615982 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.214 | BBS2 | Ivone Leong Phenotypes for gene: BBS2 were changed from Eye Disorders; Bardet-Biedl syndrome 2; Retinitis pigmentosa 74 to Eye Disorders; Bardet-Biedl syndrome 2, 615981; Retinitis pigmentosa 74, 616562 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.213 | BBS12 | Ivone Leong Phenotypes for gene: BBS12 were changed from Eye Disorders; Bardet-Biedl syndrome 12 to Eye Disorders; Bardet-Biedl syndrome 12, 615989 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.212 | BBS1 | Ivone Leong Phenotypes for gene: BBS1 were changed from Eye Disorders; Retinitis pigmentosa to Eye Disorders; Retinitis pigmentosa; Bardet-Biedl syndrome 1, 209900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.211 | BBS10 | Ivone Leong Phenotypes for gene: BBS10 were changed from Eye Disorders; Bardet-Biedl syndrome 10 to Eye Disorders; Bardet-Biedl syndrome 10, 615987 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.210 | ATOH7 | Ivone Leong Phenotypes for gene: ATOH7 were changed from Persistent hyperplastic primary vitreous, autosomal recessive; multiple ocular developmental defects, including severe vitreoretinal dysplasia, optic nerve hypoplasia, persistent fetal vasculature, microphthalmia, congenital cataracts, microcornea, corneal opacity and nystagmus to Persistent hyperplastic primary vitreous, autosomal recessive, 221900; multiple ocular developmental defects, including severe vitreoretinal dysplasia, optic nerve hypoplasia, persistent fetal vasculature, microphthalmia, congenital cataracts, microcornea, corneal opacity and nystagmus | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.209 | ATF6 | Ivone Leong Phenotypes for gene: ATF6 were changed from Achromatopsia 7 to Achromatopsia 7, 616517 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.208 | ALMS1 | Ivone Leong Phenotypes for gene: ALMS1 were changed from Eye Disorders; Alstrom syndrome to Eye Disorders; Alstrom syndrome, 203800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.207 | AHI1 | Ivone Leong Phenotypes for gene: AHI1 were changed from Eye Disorders; Joubert syndrome 17 to Eye Disorders; Joubert syndrome 3, 608629 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.206 | AGBL5 | Ivone Leong Phenotypes for gene: AGBL5 were changed from Retinitis pigmentosa; Retinitis pigmentosa 75 617023 to Retinitis pigmentosa 75, 617023 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.205 | ADAMTS18 | Ivone Leong Phenotypes for gene: ADAMTS18 were changed from Genetic Retinal Degeneration Conditions; Microcornea, myopic chorioretinal atrophy, and telecanthus to Genetic Retinal Degeneration Conditions; Microcornea, myopic chorioretinal atrophy, and telecanthus, 615458 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.204 | ADGRV1 | Ivone Leong Phenotypes for gene: ADGRV1 were changed from Usher syndrome, type 2C; Eye Disorders to Usher syndrome, type 2C, 605472; Eye Disorders; Usher syndrome, type 2C, GPR98/PDZD7 digenic, 605472 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.44 | FOXE3 | Ivone Leong Phenotypes for gene: FOXE3 were changed from {Aortic aneurysm, familial thoracic 11, susceptibility to} to Aortic aneurysm, familial thoracic 11, (susceptibility to) 617349 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.43 | FOXE3 | Ivone Leong Publications for gene: FOXE3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.42 | FLNA | Ivone Leong Phenotypes for gene: FLNA were changed from Marfan Syndrome, Thoracic Aortic Aneurysm & Dissection (TAAD), and Related Disorders to Marfan Syndrome, Thoracic Aortic Aneurysm & Dissection (TAAD), and Related Disorders; Cardiac valvular dysplasia, X-linked 314400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.41 | FLNA | Ivone Leong Publications for gene: FLNA were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.40 | FKBP14 | Ivone Leong Phenotypes for gene: FKBP14 were changed from to Ehlers-Danlos syndrome, kyphoscoliotic type, 2 614557 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.39 | FKBP14 | Ivone Leong Publications for gene: FKBP14 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.38 | ELN | Ivone Leong Publications for gene: ELN were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.37 | ABL1 | Ivone Leong Publications for gene: ABL1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.36 | LOX | Ivone Leong Publications for gene: LOX were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | ZNF469 | Ivone Leong reviewed gene: ZNF469: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | TNXB | Ivone Leong reviewed gene: TNXB: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | SLC39A13 | Ivone Leong reviewed gene: SLC39A13: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | PKD2 | Ivone Leong reviewed gene: PKD2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | PKD1 | Ivone Leong reviewed gene: PKD1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | MYLK2 | Ivone Leong reviewed gene: MYLK2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | MAT2A | Ivone Leong reviewed gene: MAT2A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | LTBP2 | Ivone Leong reviewed gene: LTBP2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | KCNN1 | Ivone Leong reviewed gene: KCNN1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | HNRNPK | Ivone Leong reviewed gene: HNRNPK: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | EMILIN1 | Ivone Leong reviewed gene: EMILIN1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | COL9A3 | Ivone Leong reviewed gene: COL9A3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | COL9A2 | Ivone Leong reviewed gene: COL9A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | COL9A1 | Ivone Leong reviewed gene: COL9A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | COL4A1 | Ivone Leong reviewed gene: COL4A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | COL2A1 | Ivone Leong reviewed gene: COL2A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | COL1A2 | Ivone Leong reviewed gene: COL1A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | COL1A1 | Ivone Leong reviewed gene: COL1A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | COL11A2 | Ivone Leong reviewed gene: COL11A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | COL11A1 | Ivone Leong reviewed gene: COL11A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | CHST14 | Ivone Leong reviewed gene: CHST14: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | B4GALT7 | Ivone Leong reviewed gene: B4GALT7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | ATP7A | Ivone Leong reviewed gene: ATP7A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | ATP6V0A2 | Ivone Leong reviewed gene: ATP6V0A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | ALDH18A1 | Ivone Leong reviewed gene: ALDH18A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | ADAMTS2 | Ivone Leong reviewed gene: ADAMTS2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | ACVR1 | Ivone Leong reviewed gene: ACVR1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | ABCC6 | Ivone Leong reviewed gene: ABCC6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | MED12 | Ivone Leong reviewed gene: MED12: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | FLCN | Ivone Leong reviewed gene: FLCN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | SMAD6 | Ivone Leong reviewed gene: SMAD6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | SMAD4 | Ivone Leong reviewed gene: SMAD4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | SMAD2 | Ivone Leong reviewed gene: SMAD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | PLOD1 | Ivone Leong reviewed gene: PLOD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | MFAP5 | Ivone Leong reviewed gene: MFAP5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | FOXE3 | Ivone Leong reviewed gene: FOXE3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | FLNA | Ivone Leong edited their review of gene: FLNA: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Amber on this panel.; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | FKBP14 | Ivone Leong reviewed gene: FKBP14: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | FBLN5 | Ivone Leong reviewed gene: FBLN5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | ELN | Ivone Leong reviewed gene: ELN: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | ABL1 | Ivone Leong reviewed gene: ABL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | TGFBR2 | Ivone Leong reviewed gene: TGFBR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | TGFBR1 | Ivone Leong reviewed gene: TGFBR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | TGFB3 | Ivone Leong edited their review of gene: TGFB3: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | TGFB2 | Ivone Leong reviewed gene: TGFB2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | SMAD3 | Ivone Leong reviewed gene: SMAD3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | SLC2A10 | Ivone Leong edited their review of gene: SLC2A10: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | SKI | Ivone Leong reviewed gene: SKI: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | PRKG1 | Ivone Leong reviewed gene: PRKG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | NOTCH1 | Ivone Leong reviewed gene: NOTCH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | MYLK | Ivone Leong reviewed gene: MYLK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | MYH11 | Ivone Leong reviewed gene: MYH11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | LOX | Ivone Leong reviewed gene: LOX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | FBN2 | Ivone Leong edited their review of gene: FBN2: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | FBN1 | Ivone Leong reviewed gene: FBN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | EFEMP2 | Ivone Leong reviewed gene: EFEMP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | COL5A2 | Ivone Leong edited their review of gene: COL5A2: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel. Therefore this gene has been promoted from Amber to Green; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | COL5A1 | Ivone Leong edited their review of gene: COL5A1: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel. Therefore this gene has been promoted from Amber to Green; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | COL3A1 | Ivone Leong reviewed gene: COL3A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | CBS | Ivone Leong edited their review of gene: CBS: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | BGN | Ivone Leong edited their review of gene: BGN: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel. Therefore this gene has been promoted from Amber to Green; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.35 | ACTA2 | Ivone Leong reviewed gene: ACTA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thoracic aortic aneurysm or dissection (GMS) v0.34 | MED12 |
Ivone Leong Source NHS GMS was added to MED12. Source Expert Review Red was added to MED12. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.34 | FLCN |
Ivone Leong Source NHS GMS was added to FLCN. Source Expert Review Red was added to FLCN. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.34 | SMAD6 |
Ivone Leong Source NHS GMS was added to SMAD6. Source Expert Review Amber was added to SMAD6. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.34 | PLOD1 |
Ivone Leong Source NHS GMS was added to PLOD1. Source Expert Review Amber was added to PLOD1. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.34 | FKBP14 |
Ivone Leong Source NHS GMS was added to FKBP14. Source Expert Review Amber was added to FKBP14. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.34 | FBLN5 |
Ivone Leong Source NHS GMS was added to FBLN5. Source Expert Review Amber was added to FBLN5. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.34 | PRKG1 |
Ivone Leong Source Expert Review Green was added to PRKG1. Source NHS GMS was added to PRKG1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.34 | NOTCH1 |
Ivone Leong Source Expert Review Green was added to NOTCH1. Source NHS GMS was added to NOTCH1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.34 | LOX |
Ivone Leong Source Expert Review Green was added to LOX. Source NHS GMS was added to LOX. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.34 | EFEMP2 |
Ivone Leong Source Expert Review Green was added to EFEMP2. Source NHS GMS was added to EFEMP2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.34 | COL5A2 |
Ivone Leong Source Expert Review Green was added to COL5A2. Source NHS GMS was added to COL5A2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.34 | COL5A1 |
Ivone Leong Source Expert Review Green was added to COL5A1. Source NHS GMS was added to COL5A1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.34 | BGN |
Ivone Leong Source Expert Review Green was added to BGN. Source NHS GMS was added to BGN. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Thoracic aortic aneurysm or dissection (GMS) v0.33 | FBLN5 | Ivone Leong Publications for gene: FBLN5 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.407 | UQCC2 | Catherine Snow Mode of inheritance for gene: UQCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | YME1L1 | Catherine Snow commented on gene: YME1L1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | TMEM65 | Catherine Snow commented on gene: TMEM65 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | TIMMDC1 | Catherine Snow commented on gene: TIMMDC1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | TFAM | Catherine Snow commented on gene: TFAM | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | SSBP1 | Catherine Snow commented on gene: SSBP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | SLC25A32 | Catherine Snow commented on gene: SLC25A32: Treatable tag was added based on reports in PMID: 26933868 and 28443623, that riboflavin treatment was effective. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | SLC25A32 | Catherine Snow commented on gene: SLC25A32 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | PTCD3 | Catherine Snow commented on gene: PTCD3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | PET117 | Catherine Snow commented on gene: PET117 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | NSUN3 | Catherine Snow changed review comment from: PMID: 27356879 - reports on a loss-of-function mutation in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency.; to: PMID: 27356879 - reports on a compound heterozygous variant resulting in a loss-of-function mutation in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | NSUN3 | Catherine Snow commented on gene: NSUN3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | MSTO1 | Catherine Snow commented on gene: MSTO1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | MRPS14 | Catherine Snow commented on gene: MRPS14 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | MRM2 | Catherine Snow changed review comment from: One proband identified in PMID: 28973171, OMIM currently based on this.; to: One proband identified in PMID: 28973171, OMIM entry currently based on this. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | MRM2 | Catherine Snow commented on gene: MRM2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | ERAL1 | Catherine Snow commented on gene: ERAL1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.406 | YME1L1 |
Catherine Snow gene: YME1L1 was added gene: YME1L1 was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: YME1L1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YME1L1 were set to 27495975 Phenotypes for gene: YME1L1 were set to ?Optic atrophy 11, 617302 |
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| Likely inborn error of metabolism v1.406 | TMEM65 |
Catherine Snow gene: TMEM65 was added gene: TMEM65 was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: TMEM65 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM65 were set to 28295037 Phenotypes for gene: TMEM65 were set to TMEM65 related mitochondrial encephalopmyopathy |
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| Likely inborn error of metabolism v1.406 | TIMMDC1 |
Catherine Snow gene: TIMMDC1 was added gene: TIMMDC1 was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: TIMMDC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TIMMDC1 were set to 28604674 Phenotypes for gene: TIMMDC1 were set to Mitochondrial complex I deficiency, nuclear type 31, 618251 |
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| Likely inborn error of metabolism v1.406 | TFAM |
Catherine Snow gene: TFAM was added gene: TFAM was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: TFAM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TFAM were set to 27448789 Phenotypes for gene: TFAM were set to ?Mitochondrial DNA depletion syndrome 15 (hepatocerebral type), 617156 |
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| Likely inborn error of metabolism v1.406 | SSBP1 |
Catherine Snow gene: SSBP1 was added gene: SSBP1 was added to Inborn errors of metabolism. Sources: Expert Review Green,Expert list Mode of inheritance for gene: SSBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SSBP1 were set to 31298765 |
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| Likely inborn error of metabolism v1.406 | SLC25A32 |
Catherine Snow gene: SLC25A32 was added gene: SLC25A32 was added to Inborn errors of metabolism. Sources: Expert Review Green,Expert list Mode of inheritance for gene: SLC25A32 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A32 were set to 26933868; 28443623 Phenotypes for gene: SLC25A32 were set to ?Exercise intolerance, riboflavin-responsive |
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| Likely inborn error of metabolism v1.406 | PTCD3 |
Catherine Snow gene: PTCD3 was added gene: PTCD3 was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: PTCD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTCD3 were set to 30607703; 30706245 Phenotypes for gene: PTCD3 were set to low birth weight, mental retardation, and optic atrophy |
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| Likely inborn error of metabolism v1.406 | PET117 |
Catherine Snow gene: PET117 was added gene: PET117 was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: PET117 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PET117 were set to 28386624 Phenotypes for gene: PET117 were set to lesions in the medulla oblongata |
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| Likely inborn error of metabolism v1.406 | NSUN3 |
Catherine Snow gene: NSUN3 was added gene: NSUN3 was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: NSUN3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NSUN3 were set to 27356879 Phenotypes for gene: NSUN3 were set to Combined mitochondrial respiratory chain complex deficiency |
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| Likely inborn error of metabolism v1.406 | MSTO1 |
Catherine Snow gene: MSTO1 was added gene: MSTO1 was added to Inborn errors of metabolism. Sources: Expert Review Green,Expert list Mode of inheritance for gene: MSTO1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: MSTO1 were set to 28554942; 28544275 Phenotypes for gene: MSTO1 were set to Myopathy, mitochondrial, and ataxia, 617675 |
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| Likely inborn error of metabolism v1.406 | MRPS14 |
Catherine Snow gene: MRPS14 was added gene: MRPS14 was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: MRPS14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRPS14 were set to 30358850 Phenotypes for gene: MRPS14 were set to ?Combined oxidative phosphorylation deficiency 38, 618378 |
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| Likely inborn error of metabolism v1.406 | MRM2 |
Catherine Snow gene: MRM2 was added gene: MRM2 was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: MRM2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRM2 were set to 28973171 Phenotypes for gene: MRM2 were set to ?Mitochondrial DNA depletion syndrome 17, 618567 |
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| Likely inborn error of metabolism v1.406 | ERAL1 |
Catherine Snow gene: ERAL1 was added gene: ERAL1 was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: ERAL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERAL1 were set to 28449065 Phenotypes for gene: ERAL1 were set to Perrault syndrome 6, 617565 |
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| Catecholaminergic polymorphic VT v1.25 | CALM3 | Ivone Leong reviewed gene: CALM3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Catecholaminergic polymorphic VT v1.25 | TECRL | Ivone Leong reviewed gene: TECRL: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Catecholaminergic polymorphic VT v1.25 | TRDN | Ivone Leong reviewed gene: TRDN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Catecholaminergic polymorphic VT v1.25 | RYR2 | Ivone Leong edited their review of gene: RYR2: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Catecholaminergic polymorphic VT v1.25 | CASQ2 | Ivone Leong reviewed gene: CASQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Catecholaminergic polymorphic VT v1.25 | CALM2 | Ivone Leong reviewed gene: CALM2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Catecholaminergic polymorphic VT v1.25 | CALM1 | Ivone Leong reviewed gene: CALM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.23 | SLC22A5 | Ivone Leong edited their review of gene: SLC22A5: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.23 | SLC22A5 | Ivone Leong edited their review of gene: SLC22A5: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Red on this panel.; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.23 | SLC4A3 | Ivone Leong edited their review of gene: SLC4A3: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Amber on this panel.; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.23 | CACNB2 | Ivone Leong edited their review of gene: CACNB2: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Amber on this panel.; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.23 | CACNA2D1 | Ivone Leong edited their review of gene: CACNA2D1: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Amber on this panel.; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.23 | KCNQ1 | Ivone Leong reviewed gene: KCNQ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.23 | KCNJ2 | Ivone Leong edited their review of gene: KCNJ2: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.23 | KCNH2 | Ivone Leong reviewed gene: KCNH2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Short QT syndrome v1.23 | CACNA1C | Ivone Leong reviewed gene: CACNA1C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Brugada syndrome and cardiac sodium channel disease v1.45 | SCN5A | Ivone Leong edited their review of gene: SCN5A: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.45 | CALM3 | Ivone Leong Mode of inheritance for gene: CALM3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | CAV3 | Ivone Leong reviewed gene: CAV3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | KCNJ5 | Ivone Leong reviewed gene: KCNJ5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | SCN4B | Ivone Leong reviewed gene: SCN4B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | ANK2 | Ivone Leong reviewed gene: ANK2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | SCN5A | Ivone Leong edited their review of gene: SCN5A: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | KCNQ1 | Ivone Leong edited their review of gene: KCNQ1: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | KCNJ2 | Ivone Leong reviewed gene: KCNJ2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | KCNH2 | Ivone Leong reviewed gene: KCNH2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | KCNE2 | Ivone Leong reviewed gene: KCNE2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | KCNE1 | Ivone Leong edited their review of gene: KCNE1: Added comment: Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | CALM3 | Ivone Leong reviewed gene: CALM3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | CALM2 | Ivone Leong reviewed gene: CALM2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | CALM1 | Ivone Leong reviewed gene: CALM1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.44 | CACNA1C | Ivone Leong reviewed gene: CACNA1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Long QT syndrome v1.43 | TECRL |
Ivone Leong gene: TECRL was added gene: TECRL was added to Long QT syndrome. Sources: NHS GMS Mode of inheritance for gene: TECRL was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TECRL were set to Ventricular tachycardia, catecholaminergic polymorphic, 3, 614021 Review for gene: TECRL was set to AMBER Added comment: New gene submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Amber on this panel. Sources: NHS GMS |
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| Likely inborn error of metabolism v1.405 | COASY | Catherine Snow Classified gene: COASY as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.405 | COASY | Catherine Snow Gene: coasy has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.405 | COASY | Catherine Snow Classified gene: COASY as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.405 | COASY | Catherine Snow Gene: coasy has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.405 | COASY | Catherine Snow Classified gene: COASY as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.405 | COASY | Catherine Snow Gene: coasy has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.404 | COASY |
Catherine Snow gene: COASY was added gene: COASY was added to Inborn errors of metabolism. Sources: Expert list Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COASY were set to 30089828 Phenotypes for gene: COASY were set to Neurodegeneration with brain iron accumulation 6, 615643; Pontocerebellar hypoplasia, type 12, 618266 Review for gene: COASY was set to AMBER Added comment: COASY has sufficient evidence to be made Green however as it has been purposefully not rated by experts as Green on Mitochondrial Panels COASY will be rated as Amber. Sources: Expert list |
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| Likely inborn error of metabolism v1.403 | MRPS7 | Catherine Snow Publications for gene: MRPS7 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.402 | MRPS7 | Catherine Snow Mode of inheritance for gene: MRPS7 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.402 | MRPS7 | Catherine Snow Mode of inheritance for gene: MRPS7 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.402 | MRPS7 | Catherine Snow Mode of inheritance for gene: MRPS7 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.402 | MRPS7 | Catherine Snow Mode of inheritance for gene: MRPS7 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.402 | MRPS7 | Catherine Snow Mode of inheritance for gene: MRPS7 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.402 | MRPS7 | Catherine Snow Mode of inheritance for gene: MRPS7 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.401 | MRPS7 | Catherine Snow Classified gene: MRPS7 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.401 | MRPS7 | Catherine Snow Gene: mrps7 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.401 | MRPS7 | Catherine Snow Mode of inheritance for gene: MRPS7 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.401 | MRPS7 | Catherine Snow Mode of inheritance for gene: MRPS7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.401 | MRPS7 | Catherine Snow Classified gene: MRPS7 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.401 | MRPS7 | Catherine Snow Gene: mrps7 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.400 | UQCC3 | Catherine Snow Publications for gene: UQCC3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.400 | UQCC3 | Catherine Snow changed review comment from: Comment on list classification: Promoting to Amber as some evidence is avaliable; to: Comment on list classification: Promoting to Amber as some evidence is available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.400 | UQCC3 | Catherine Snow Mode of inheritance for gene: UQCC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.399 | UQCC3 | Catherine Snow Classified gene: UQCC3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.399 | UQCC3 | Catherine Snow Gene: uqcc3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.399 | UQCC3 | Catherine Snow Classified gene: UQCC3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.399 | UQCC3 | Catherine Snow Added comment: Comment on list classification: Promoting to Amber as some evidence is avaliable | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.399 | UQCC3 | Catherine Snow Gene: uqcc3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.398 | UQCC2 | Catherine Snow Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1098 | ZNF292 |
Konstantinos Varvagiannis gene: ZNF292 was added gene: ZNF292 was added to Intellectual disability. Sources: Radboud University Medical Center, Nijmegen,Literature Mode of inheritance for gene: ZNF292 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ZNF292 were set to 31723249; 29904178 Phenotypes for gene: ZNF292 were set to Intellectual disability; Autism; Attention deficit hyperactivity disorder; Abnormality of the face; Abnormal muscle tone; Abnormality of nervous system morphology; Growth abnormality; Feeding difficulties; Abnormality of the skeletal system; Abnormality of the cardiovascular system; Microcephaly; Seizures Penetrance for gene: ZNF292 were set to Incomplete Review for gene: ZNF292 was set to GREEN gene: ZNF292 was marked as current diagnostic Added comment: Mirzaa et al. (2019 - PMID: 31723249) report on 28 individuals (from 27 families) with putatively pathogenic ZNF292 variants. Main features consisted of DD and ID (27/28 - mild in 40%, moderate in 22%, severe in 11%) with or without ASD and ADHD. A single individual had no evidence of ID but had speech delay and ASD at the age of 6. Additional features (by diminishing order of frequency) included presence of non-specific dysmorphic features (~45%), abnormal tone, brain MRI abnormalities, growth failure, feeding difficulties, skeletal and cardiac anomalies, microcephaly and epilepsy (~11%). As the authors comment, ZNF292 encodes a zinc finger protein, acting as a transcription factor. Evidence is provided that gene has high expression in the developing human brain, with its expression being higher in prenatal development and diminishing postnatally. Znf292 is also expressed in adult mouse brain (highest in hippocampus/Purkinje cells). Variants were identified by exome or targeted panel sequencing (targeted capture/molecular inversion probes). Previous investigations (eg. aCGH, analysis of relevant genes) had probably ruled out alternative causes in most with few having VUS or possibly relevant additional variants (eg. a KDM5C stopgain variant in a male). 24 putatively pathogenic variants were observed in this cohort, all predicting LoF (stopgain, frameshift or splice variants). All were de novo with the exception of one family where the variant was inherited from an affected parent. Almost all were absent from gnomAD and had CADD scores > 35. Most variants lied within the last and largest exon that encodes a DNA binding domain. RT-PCR on RNA from 2 individuals harboring such variants confirmed that NMD does not apply. This exon however represents ~88% of the total coding length so the distribution of variants in this (NMD escaping) region was consistent with what would also be expected by chance. ZNF292 has a pLI of 1 in gnomAD. Manual review of some relevant LoF variants in gnomAD suggested that they represent false positive calls. As a result, the effect of variants is not clear although haploinsufficiency is still possible based also on phenotype of (larger) deletions spanning this gene (cited: Engwerda et al - PMID: 29904178 / The study focuses on deletions of the broader 6q. A possible role of ZNF292 is discussed as autism was present in 4/10 individuals with deletions encompassing this gene). Based on the aforementioned cohort with one individual being diagnosed with mild ID only as an adult and/or presence of 5 pLoF variants in gnomAD the authors propose that some variants may be incompletely penetrant or associated with only mild features. Finally, 15 additional individuals (belonging to 12 families) harbored variants for which pathogenicity was suspected (but could not be concluded) due to insufficient phenotypic information, lack of sufficient parental studies or missense variants. In this cohort variants were mostly pLoF, while 3 individuals (incl. 2 sibs) had a de novo missense SNV. ------ Other studies were not here reviewed as some of the individuals reported were published previously in larger cohorts. ------ There is no associated phenotype in OMIM / G2P. SysID includes this gene among the candidate ID ones. ZNF292 is included in gene panels for ID offered by some diagnostic laboratories (incl. Radboudumc and GeneDx). ------ Overall ZNF292 could be added to the ID panel probably with green (or amber) rating. [Please consider inclusion in other possibly relevant panels eg. autism, epilepsy] Sources: Radboud University Medical Center, Nijmegen, Literature |
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| Skeletal dysplasia v1.216 | PIK3C2A | Eleanor Williams Classified gene: PIK3C2A as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.216 | PIK3C2A | Eleanor Williams Added comment: Comment on list classification: After further assessment of the phenotype in the supplementary data for PMID: 31034465 (scoliosis, short stature etc) it was decided to promote this gene to green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.216 | PIK3C2A | Eleanor Williams Gene: pik3c2a has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.215 | TMEM67 | Eleanor Williams Classified gene: TMEM67 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.215 | TMEM67 | Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team demoting this gene to red as the skeletal phenotype is not strong. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.215 | TMEM67 | Eleanor Williams Gene: tmem67 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.214 | KIAA0753 | Eleanor Williams Classified gene: KIAA0753 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.214 | KIAA0753 | Eleanor Williams Added comment: Comment on list classification: Adding this ciliopathy gene to the skeletal dysplasia panel after consultation with the Genomics England clinical team. The reported phenotypes include skeletal dysplasias. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.214 | KIAA0753 | Eleanor Williams Gene: kiaa0753 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.213 | KIAA0753 |
Eleanor Williams gene: KIAA0753 was added gene: KIAA0753 was added to Skeletal dysplasia. Sources: Other Mode of inheritance for gene: KIAA0753 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIAA0753 were set to 29138412; 28220259; 26643951 Phenotypes for gene: KIAA0753 were set to ?Orofaciodigital syndrome XV 617127; Joubert syndrome; Short-rib skeletal dysplasia Review for gene: KIAA0753 was set to GREEN Added comment: Provisionally associated with ?Orofaciodigital syndrome XV (617127) in OMIM PMID: 26643951 - Chevrier et al 2016 - 1 case of a newborn female presenting with an oral-facial-digital (OFD) VI syndrome in which they identified two causal heterozygous mutations in the KIAA0753 gene. Both KIAA0753 mutations, one nonsense variant (c.1891A>T; p.Lys631*) and one substitution in Intron 8 (c.1546-3C>A), were confirmed by Sanger sequencing, as well as the maternal heterozygous status for the non-sense variant. PMID: 28220259 - Stephen et al 2017 - 2 siblings with Joubert syndrome associated with growth hormone deficiency but no oral or digital anomalies. Whole exome sequencing of the family identified compound heterozygous mutations in KIAA0753, i.e., a missense mutation (p.Arg257Gly) and an intronic mutation (c.2359-1G>C). PMID: 29138412 - Hammarsjö et al 2017 - report biallelic pathogenic variants in KIAA0753 in four patients from 3 families with short-rib type skeletal dysplasia - ranging from prenatal lethality in one fetus to viability with moderate skeletal dysplasia in three children. 2 families had the same homozygous nonsense variant but are not thought to be related. In the 3rd family the index patient was compound heterogyzous. KIAA0753 is expressed in normal fetal human growth plate and they show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning. In family 1, they also identified an additional homozygous missense variant, c.425 C > T (p.Thr142Met) in SLC13A5 and conclude that the seizures and teeth hypoplasia in P1 and P2 are due to the homozygous SLC13A5 variant. Sources: Other |
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| Skeletal dysplasia v1.212 | ZSWIM6 | Eleanor Williams Classified gene: ZSWIM6 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.212 | ZSWIM6 | Eleanor Williams Added comment: Comment on list classification: This cililiopathy gene has been added to the skeletal dysplasia panel after consultation with the Genomics England clinical team. There is sufficient skeletal involvement to include on this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.212 | ZSWIM6 | Eleanor Williams Gene: zswim6 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.211 | ZSWIM6 |
Eleanor Williams gene: ZSWIM6 was added gene: ZSWIM6 was added to Skeletal dysplasia. Sources: Other Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZSWIM6 were set to 25105228 Phenotypes for gene: ZSWIM6 were set to Acromelic frontonasal dysostosis 603671 Review for gene: ZSWIM6 was set to GREEN Added comment: Associated with Acromelic frontonasal dysostosis #603671 (AD) and Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features #617865 (AD) in OMIM. Acromelic frontonasal dysostosis - OMIM lists the skeletal phenotypes of Patellar hypoplasia or aplasia (in some patients), Tibial hypoplasia, polydactyly of hands and feet, Talipes equinovarus. Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features - OMIM lists the skeletal phenotype of Foot deformities (in some patients) only Sources: Other |
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| Skeletal dysplasia v1.210 | DHCR7 | Eleanor Williams Classified gene: DHCR7 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.210 | DHCR7 | Eleanor Williams Added comment: Comment on list classification: This ciliopathy gene is being added to the Skeletal dysplasia panel after discussion with the Genomics England clinical team. Smith-Lemli-Optiz syndrome includes features such as limb shortening as well as abnormalities of the hands and feet. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.210 | DHCR7 | Eleanor Williams Gene: dhcr7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.209 | DHCR7 |
Eleanor Williams gene: DHCR7 was added gene: DHCR7 was added to Skeletal dysplasia. Sources: Other Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DHCR7 were set to 9634533 Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome 270400 Review for gene: DHCR7 was set to GREEN Added comment: Associated with Smith-Lemli-Opitz syndrome in OMIM. They describe this as "an autosomal recessive multiple congenital malformation and mental retardation syndrome." Several skeletal features are listed in the clinical features in OMIM including limb shortening, Hip dislocation and subluxation, and abnormalities of the hands and feet. Sources: Other |
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| Skeletal ciliopathies v0.19 | KIAA0753 |
Eleanor Williams changed review comment from: Provisionally associated with ?Orofaciodigital syndrome XV (617127) in OMIM PMID: 26643951 - Chevrier et al 2016 - 1 case of a newborn female presenting with an oral-facial-digital (OFD) VI syndrome in which they identified two causal heterozygous mutations in the KIAA0753 gene. Both KIAA0753 mutations, one nonsense variant (c.1891A>T; p.Lys631*) and one substitution in Intron 8 (c.1546-3C>A), were confirmed by Sanger sequencing, as well as the maternal heterozygous status for the non-sense variant. The sporadic occurrence of the c.1546-3C>A variant was confirmed by samples concordance. cDNA analysis indicates the intronic variant results in skipping of Exon 8 that caused a frameshift, changed the amino acids sequence and led to the occurrence of a premature stop codon. Because both mutations appeared truncating and probably compound heterozygous, they were considered as potentially causal. PMID: 28220259 - Stephen et al 2017 - 2 siblings with Joubert syndrome associated with growth hormone deficiency. Whole exome sequencing of the family identified compound heterozygous mutations in KIAA0753, i.e., a missense mutation (p.Arg257Gly) and an intronic mutation (c.2359-1G>C). Brain MRI of the younger sibling revealed the “molar tooth sign”, and she had global developmental delay. The older sibling was diagnosed after the younger sibling, and brain MRI showed an ectopic posterior pituitary gland in addition to the molar tooth sign. Hypotonia and global developmental delay were noted at 10 months. The parents were each heterozygous for one of the variants. Cilia formation in primary fibroblasts from patients was signficantly lower than in controls. PMID: 29138412 - Hammarsjö et al 2017 - report biallelic pathogenic variants in KIAA0753 in four patients from 3 families with short-rib type skeletal dysplasia - ranging from prenatal lethality in one fetus to viability with moderate skeletal dysplasia in three children. 2 families had the same homozygous nonsense variant but are not thought to be related. In the 3rd family the index patient was compound heterogyzous. KIAA0753 is expressed in normal fetal human growth plate and they show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning. In family 1, they also identified an additional homozygous missense variant, c.425 C > T (p.Thr142Met) in SLC13A5 and conclude that the seizures and teeth hypoplasia in P1 and P2 are due to the homozygous SLC13A5 variant. ; to: Provisionally associated with ?Orofaciodigital syndrome XV (617127) in OMIM PMID: 26643951 - Chevrier et al 2016 - 1 case of a newborn female presenting with an oral-facial-digital (OFD) VI syndrome in which they identified two causal heterozygous mutations in the KIAA0753 gene. Both KIAA0753 mutations, one nonsense variant (c.1891A>T; p.Lys631*) and one substitution in Intron 8 (c.1546-3C>A), were confirmed by Sanger sequencing, as well as the maternal heterozygous status for the non-sense variant. The sporadic occurrence of the c.1546-3C>A variant was confirmed by samples concordance. cDNA analysis indicates the intronic variant results in skipping of Exon 8 that caused a frameshift, changed the amino acids sequence and led to the occurrence of a premature stop codon. Because both mutations appeared truncating and probably compound heterozygous, they were considered as potentially causal. PMID: 28220259 - Stephen et al 2017 - 2 siblings with Joubert syndrome associated with growth hormone deficiency but no oral or digital anomalies. Whole exome sequencing of the family identified compound heterozygous mutations in KIAA0753, i.e., a missense mutation (p.Arg257Gly) and an intronic mutation (c.2359-1G>C). Brain MRI of the younger sibling revealed the “molar tooth sign”, and she had global developmental delay. The older sibling was diagnosed after the younger sibling, and brain MRI showed an ectopic posterior pituitary gland in addition to the molar tooth sign. Hypotonia and global developmental delay were noted at 10 months. The parents were each heterozygous for one of the variants. Cilia formation in primary fibroblasts from patients was signficantly lower than in controls. PMID: 29138412 - Hammarsjö et al 2017 - report biallelic pathogenic variants in KIAA0753 in four patients from 3 families with short-rib type skeletal dysplasia - ranging from prenatal lethality in one fetus to viability with moderate skeletal dysplasia in three children. 2 families had the same homozygous nonsense variant but are not thought to be related. In the 3rd family the index patient was compound heterogyzous. KIAA0753 is expressed in normal fetal human growth plate and they show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning. In family 1, they also identified an additional homozygous missense variant, c.425 C > T (p.Thr142Met) in SLC13A5 and conclude that the seizures and teeth hypoplasia in P1 and P2 are due to the homozygous SLC13A5 variant. |
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| Skeletal ciliopathies v0.19 | PMM2 | Eleanor Williams commented on gene: PMM2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.19 | TXNDC15 | Eleanor Williams Classified gene: TXNDC15 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.19 | TXNDC15 | Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team, removing this gene from the skeletal ciliopathies panel as the skeletal phenotype is polydactyly only. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.19 | TXNDC15 | Eleanor Williams Gene: txndc15 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.18 | SCLT1 | Eleanor Williams Classified gene: SCLT1 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.18 | SCLT1 | Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team, removing this gene from the skeletal ciliopathies panel as the skeletal phenotype is not strong. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.18 | SCLT1 | Eleanor Williams Gene: sclt1 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.17 | DDX59 | Eleanor Williams Classified gene: DDX59 as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.17 | DDX59 | Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team, removing this gene from the skeletal ciliopathies panel as the skeletal phenotype is mainly polydactyly. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.17 | DDX59 | Eleanor Williams Gene: ddx59 has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.16 | CENPF | Eleanor Williams Classified gene: CENPF as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.16 | CENPF | Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team, removing this gene from the skeletal ciliopathies panel as the phenotype is polydactyly only. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.16 | CENPF | Eleanor Williams Gene: cenpf has been removed from the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.4 | PIK3C2A |
Eleanor Williams gene: PIK3C2A was added gene: PIK3C2A was added to Hearing loss. Sources: Literature Mode of inheritance for gene: PIK3C2A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIK3C2A were set to 31034465 Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome 618440 Review for gene: PIK3C2A was set to AMBER Added comment: Associated with Oculoskeletodental syndrome 618440 (AR) in OMIM based on evidence from PMID: 31034465 - Tiosano et al 2019 - report 5 individuals from 3 unrelated consanguineous families with a similar set of clinical features including dysmorphic facial features, short stature, skeletal and neurological abnormalities, and cataracts. 3 out 5 indviduals (one from each family) showed hearing loss (non-progressive hearing deficiency, bilateral moderate conductive hearing loss and sensorineural hearing loss, hearing aids at 22 years old). Homozygous loss-of-function mutations in PIK3C2A were identified in each family. Sources: Literature |
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| Skeletal dysplasia v1.208 | PIK3C2A | Eleanor Williams Phenotypes for gene: PIK3C2A were changed from to Oculoskeletodental syndrome 618440 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.207 | PIK3C2A | Eleanor Williams Classified gene: PIK3C2A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.207 | PIK3C2A | Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team, decided to rate this gene Amber for now. Not clear how relevant the skeletal phenotypes are to this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.207 | PIK3C2A | Eleanor Williams Gene: pik3c2a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.206 | PIK3C2A |
Eleanor Williams gene: PIK3C2A was added gene: PIK3C2A was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: PIK3C2A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIK3C2A were set to 31034465 Review for gene: PIK3C2A was set to AMBER Added comment: Associated with Oculoskeletodental syndrome #618440 (AR) in OMIM. This is based on evidence from PMID: 31034465 - Tiosano et al 2019 - report 5 individuals from 3 unrelated consanguineous families with a similar set of clinical features including dysmorphic facial features, short stature, skeletal and neurological abnormalities, and cataracts. The skeletal findings included "scoliosis, delayed bone age, diminished ossification of femoral heads, cervical lordosis, shortened fifth digits with mild metaphyseal dysplasia and clinodactyly". Homozygous loss-of-function mutations in PIK3C2A were identified in each family. Sources: Literature |
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| Skeletal dysplasia v1.205 | RPL13 |
Eleanor Williams changed review comment from: PMID: 31630789 - Le Caignec et al 2019 - report one de novo missense variant (c.548G>C [p.Arg183Pro]) and three de novo splice variants in RPL13, which encodes ribosomal protein RPL13, in four unrelated individuals with a rare bone dysplasia causing severe short stature. The three splice variants (c.477þ1G>T, c.477þ1G>A, and c.477þ2 T>C) result in partial intron retention, which leads to an 18-amino acid insertion. Sources: Literature; to: Not associated with a phenotype in OMIM or Gene2Phenotype. PMID: 31630789 - Le Caignec et al 2019 - report one de novo missense variant (c.548G>C [p.Arg183Pro]) and three de novo splice variants in RPL13, which encodes ribosomal protein RPL13, in four unrelated individuals with a rare bone dysplasia causing severe short stature. The three splice variants (c.477þ1G>T, c.477þ1G>A, and c.477þ2 T>C) result in partial intron retention, which leads to an 18-amino acid insertion. Sources: Literature |
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| Skeletal dysplasia v1.205 | RPL13 | Eleanor Williams Classified gene: RPL13 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.205 | RPL13 | Eleanor Williams Added comment: Comment on list classification: Promoting this gene to green as 4 cases, one with a missense variant but 3 with splice variants that lead to an 18 amino acid insertion in the protein have been reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.205 | RPL13 | Eleanor Williams Gene: rpl13 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.398 | UQCC2 | Catherine Snow Classified gene: UQCC2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.398 | UQCC2 | Catherine Snow Added comment: Comment on list classification: This gene was promoted from Amber to Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter. Two unrelated cases reported, with functional supporting evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.398 | UQCC2 | Catherine Snow Gene: uqcc2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.397 | UQCC2 | Catherine Snow Publications for gene: UQCC2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.397 | UQCC2 | Catherine Snow Classified gene: UQCC2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.397 | UQCC2 | Catherine Snow Added comment: Comment on list classification: This gene was promoted from Amber to Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter. Two unrelated cases reported, with functional supporting evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.397 | UQCC2 | Catherine Snow Gene: uqcc2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.396 | UQCC2 | Catherine Snow Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.15 | ZSWIM6 | Eleanor Williams commented on gene: ZSWIM6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.15 | SCLT1 |
Eleanor Williams changed review comment from: Not associated with any phenotype in OMIM or Gene2Phenotype. PMID: 15797711 - this paper does not appear to be about SCLT1 or ciliopathies PMID: 23348840 - Tanos et al 2013 - identified SCLT1 as a component of distal appendages (DAPs) of centrioles that have been proposed to anchor cilia to the plasma membrane. It is one of five DAP components and is essential for ciliogenesis. PMID: 24285566 - Adly et al 2014 - 1 case with index patient with consanguineous Saudi parents and a severe ciliopathy phenotype. He had severe midline cleft lip and palate, microcephaly and choanal atresia. He also had significant eye involvement in the form of severe coloboma, and congenital heart disease (ASD and VSD). He had micropenis. Brain imaging revealed pachygyria and absent corpus callosum. He had abnormal inner ear structures. A splicing mutation was identified in SCLT1 (, NM_144643.2:exon5:c.290+2T>C). This mutation completely abolishes the consensus donor site of exon 5 as confirmed by RTPCR, which showed complete skipping of exon 5 resulting in a frameshift and introduction of a premature stop codon (p.Lys79Valfs*4), PMID: 28005958 - de Castro-Miró et al 2016 - A cohort of 33 pedigrees affected with a variety of retinal disorders was analysed by WES. 1 case with compound heterozygosity (one missense and one splicing altering mutations) in SCLT1 that segregates with the condition in the family (2 affected siblings). Proposed to be causative of early-onset Retinitis Pigmentosa. SCLT1 is a member of the centrosomal/ciliary protein family. PMID: 28486600 - Li et al 2017 - report a mouse model with mutated Sclt1 gene. The Sclt1-/- mice exhibit typical ciliopathy phenotypes, including cystic kidney, cleft palate and polydactyly. PMID: 30425282 - Katagiri et al 2018 - a patient with Senior Løken syndrome and her unaffected parents revealed that the patient had infantile-onset retinal dystrophy and juvenile-onset nephronophthisis. Other systemic abnormalities included hepatic dysfunction, megacystis, mild learning disability, autism, obesity, and hyperinsulinemia. Whole-exome sequencing identified compound heterozygous SCLT1 variants (c.1218 + 3insT and c.1631A > G) in the patient. The unaffected parents were heterozygous for each variant. Transcript analysis using reverse transcription PCR demonstrated that the c.1218 + 3insT variant leads to exon 14 skipping (p.V383_M406del), while the other variant (c.1631A > G) primarily leads to exon 17 skipping (p.D480EfsX11) as well as minor amounts of two transcripts. Immunohistochemical analysis demonstrated that the Sclt1 protein was localized to the distal appendage of the photoreceptor basal body, indicating a ciliary protein. 3 cases plus a mouse model and functional evidence that the protein is a ciliary protein.; to: Not associated with any phenotype in OMIM or Gene2Phenotype. PMID: 15797711 - this paper does not appear to be about SCLT1 or ciliopathies PMID: 23348840 - Tanos et al 2013 - identified SCLT1 as a component of distal appendages (DAPs) of centrioles that have been proposed to anchor cilia to the plasma membrane. It is one of five DAP components and is essential for ciliogenesis. PMID: 24285566 - Adly et al 2014 - 1 case with index patient with consanguineous Saudi parents and a severe ciliopathy phenotype consistent with oro-facio-digital syndrome type IX. He had severe midline cleft lip and palate, microcephaly and choanal atresia. He also had significant eye involvement in the form of severe coloboma, and congenital heart disease (ASD and VSD). He had micropenis. Brain imaging revealed pachygyria and absent corpus callosum. He had abnormal inner ear structures. A splicing mutation was identified in SCLT1 (, NM_144643.2:exon5:c.290+2T>C). This mutation completely abolishes the consensus donor site of exon 5 as confirmed by RTPCR, which showed complete skipping of exon 5 resulting in a frameshift and introduction of a premature stop codon (p.Lys79Valfs*4), PMID: 28005958 - de Castro-Miró et al 2016 - A cohort of 33 pedigrees affected with a variety of retinal disorders was analysed by WES. 1 case with compound heterozygosity (one missense and one splicing altering mutations) in SCLT1 that segregates with the condition in the family (2 affected siblings). Proposed to be causative of early-onset Retinitis Pigmentosa. SCLT1 is a member of the centrosomal/ciliary protein family. PMID: 28486600 - Li et al 2017 - report a mouse model with mutated Sclt1 gene. The Sclt1-/- mice exhibit typical ciliopathy phenotypes, including cystic kidney, cleft palate and polydactyly. PMID: 30425282 - Katagiri et al 2018 - a patient with Senior Løken syndrome and her unaffected parents revealed that the patient had infantile-onset retinal dystrophy and juvenile-onset nephronophthisis. Other systemic abnormalities included hepatic dysfunction, megacystis, mild learning disability, autism, obesity, and hyperinsulinemia. Whole-exome sequencing identified compound heterozygous SCLT1 variants (c.1218 + 3insT and c.1631A > G) in the patient. The unaffected parents were heterozygous for each variant. Transcript analysis using reverse transcription PCR demonstrated that the c.1218 + 3insT variant leads to exon 14 skipping (p.V383_M406del), while the other variant (c.1631A > G) primarily leads to exon 17 skipping (p.D480EfsX11) as well as minor amounts of two transcripts. Immunohistochemical analysis demonstrated that the Sclt1 protein was localized to the distal appendage of the photoreceptor basal body, indicating a ciliary protein. 3 cases plus a mouse model and functional evidence that the protein is a ciliary protein. |
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| Skeletal ciliopathies v0.15 | LZTFL1 | Eleanor Williams commented on gene: LZTFL1: Associated with Bardet-Biedl syndrome 17 #615994 (AR) in OMIM with polydactyly of hands and feet listed as clinical features. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.15 | DHCR7 | Eleanor Williams commented on gene: DHCR7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.396 | SLC25A4 | Catherine Snow Added comment: Comment on mode of inheritance: The MOI was changed for consistency between panels Mitochondrial DNA maintenance disorder (code: 533) and Possible mitochondrial disorder - nuclear genes (code: 539). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.396 | SLC25A4 | Catherine Snow Mode of inheritance for gene: SLC25A4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.395 | ABCB7 | Catherine Snow Added comment: Comment on mode of inheritance: Changed MOI for consistency amongst other panels. XLR in OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.395 | ABCB7 | Catherine Snow Mode of inheritance for gene: ABCB7 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v0.15 | CENPF | Eleanor Williams commented on gene: CENPF | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.395 | ABCB7 | Catherine Snow Added comment: Comment on mode of inheritance: Changed MOI for consistency amongst other panels. XLR in OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.395 | ABCB7 | Catherine Snow Mode of inheritance for gene: ABCB7 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.51 | SLC9A3R1 | Eleanor Williams Classified gene: SLC9A3R1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.51 | SLC9A3R1 | Eleanor Williams Added comment: Comment on list classification: Changing the rating of this gene to Amber in light of the expert review that highlights that the proposed pathogenic variants are found at higher than expected frequency in the general population. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.51 | SLC9A3R1 | Eleanor Williams Gene: slc9a3r1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Non-syndromic familial congenital anorectal malformations v1.6 | Rebecca Foulger Panel types changed to Rare Disease 100K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| VACTERL-like phenotypes v1.25 | Rebecca Foulger Panel types changed to Rare Disease 100K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.50 | SLC9A3R1 |
Detlef Bockenhauer changed review comment from: In the original publication (PMID: 18784102 - Karim et al 2008), Karim et al examine 159 patients with either nephrolithiasis or bone demineralisation. They find variants in SLC9A3R1 in 4 patients from 3 families. These 3 variants are now listed in gnomAD with a combined frequency of just over 2%. Thus, the frequency of these variants in the patient cohort is essentially the same as in the general population. Several publications subsequently report variants in this gene in cohorts with nephrolithiasis/calcinosis, but again essentially with either the same or even lower frequency as in the normal population: 1) Daga et al (Kidney Int. 2018 Jan;93(1):204-213. doi: 10.1016/j.kint.2017.06.025): 1 out of 51 families 2) Braun et al (Clin J Am Soc Nephrol. 2016 Apr 7;11(4):664-72. doi: 10.2215/CJN.07540715): 1 out of 143 3) Halbritter et al (J Am Soc Nephrol. 2015 Mar; 26(3): 543–551doi: 10.1681/ASN.2014040388): 2 out of 268 Thus, there are several lines of evidence arguing against SLC9A3R1 being a disease causing gene: 1) the frequency of variants in SLC9A3R in itself higher than expected for a dominant disease gene (3% combined frequency of missense and pLoF in gnomAD) 2) there are 231 missende variants in this gene listed in gnomAD versus 211.7 expected, based on gene length (Z=-0.48), thus the gene is not constrained against missense variants 3) the frequency of variants in patients with nephrolithiasis/calcinosis is essentially the same as in the general population The clinical relevance of any variants identified in SLC9A3R1 is thus questionable.; to: In the original publication (PMID: 18784102 - Karim et al 2008), Karim et al examine 159 patients with either nephrolithiasis or bone demineralisation. They find variants in SLC9A3R1 in 4 patients from 3 families. These 3 variants are now listed in gnomAD with a combined frequency of just over 2%. Thus, the frequency of these variants in the patient cohort is essentially the same as in the general population. Several publications subsequently report variants in this gene in cohorts with nephrolithiasis/calcinosis, but again essentially with either the same or even lower frequency as in the normal population: 1) Daga et al (Kidney Int. 2018 Jan;93(1):204-213. doi: 10.1016/j.kint.2017.06.025): 1 out of 51 families 2) Braun et al (Clin J Am Soc Nephrol. 2016 Apr 7;11(4):664-72. doi: 10.2215/CJN.07540715): 1 out of 143 3) Halbritter et al (J Am Soc Nephrol. 2015 Mar; 26(3): 543–551doi: 10.1681/ASN.2014040388): 2 out of 268 Thus, there are several lines of evidence arguing against SLC9A3R1 being a disease causing gene: 1) the frequency of variants in SLC9A3R in itself is higher than expected for a dominant disease gene (3% combined frequency of missense and pLoF in gnomAD) 2) there are 231 missense variants in this gene listed in gnomAD versus 211.7 expected, based on gene length (Z=-0.48), thus the gene is not constrained against missense variants 3) the frequency of variants in patients with nephrolithiasis/calcinosis is essentially the same as in the general population The clinical relevance of any variants identified in SLC9A3R1 is thus questionable. |
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| Nephrocalcinosis or nephrolithiasis v1.50 | SLC9A3R1 |
Detlef Bockenhauer changed review comment from: In the original publication (PMID: 18784102 - Karim et al 2008), Karim et al examine 159 patients with either nephrolithiasis or bone demineralisation. they find variants in SLC9A3R1 in 4 patients from 3 families. These variants are now listed in gnomAD with a combined frequency of just over 2%. Thus, the frequency of these variants in the patient cohort is essentially the same as in the general population. Several publications subsequently report variants in this gene in cohorts with nephrolithiasis/calcinosis, but again essentially with either the same or even lower frequency as in the normal population: 1) Daga et al (Kidney Int. 2018 Jan;93(1):204-213. doi: 10.1016/j.kint.2017.06.025): 1 out of 51 families 2) Braun et al (Clin J Am Soc Nephrol. 2016 Apr 7;11(4):664-72. doi: 10.2215/CJN.07540715): 1 out of 143 3) Halbritter et al (J Am Soc Nephrol. 2015 Mar; 26(3): 543–551doi: 10.1681/ASN.2014040388): 2 out of 268 Thus, not only is the frequency of variants in SLC9A3R in itself higher than expected for a dominant disease gene, but the frequency of variants in patients with nephrolithiasis/calcinosis is essentially the same as in the general population and the likelihood that they disease causing is thus very unlikely.; to: In the original publication (PMID: 18784102 - Karim et al 2008), Karim et al examine 159 patients with either nephrolithiasis or bone demineralisation. They find variants in SLC9A3R1 in 4 patients from 3 families. These 3 variants are now listed in gnomAD with a combined frequency of just over 2%. Thus, the frequency of these variants in the patient cohort is essentially the same as in the general population. Several publications subsequently report variants in this gene in cohorts with nephrolithiasis/calcinosis, but again essentially with either the same or even lower frequency as in the normal population: 1) Daga et al (Kidney Int. 2018 Jan;93(1):204-213. doi: 10.1016/j.kint.2017.06.025): 1 out of 51 families 2) Braun et al (Clin J Am Soc Nephrol. 2016 Apr 7;11(4):664-72. doi: 10.2215/CJN.07540715): 1 out of 143 3) Halbritter et al (J Am Soc Nephrol. 2015 Mar; 26(3): 543–551doi: 10.1681/ASN.2014040388): 2 out of 268 Thus, there are several lines of evidence arguing against SLC9A3R1 being a disease causing gene: 1) the frequency of variants in SLC9A3R in itself higher than expected for a dominant disease gene (3% combined frequency of missense and pLoF in gnomAD) 2) there are 231 missende variants in this gene listed in gnomAD versus 211.7 expected, based on gene length (Z=-0.48), thus the gene is not constrained against missense variants 3) the frequency of variants in patients with nephrolithiasis/calcinosis is essentially the same as in the general population The clinical relevance of any variants identified in SLC9A3R1 is thus questionable. |
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| Nephrocalcinosis or nephrolithiasis v1.50 | SLC9A3R1 | Detlef Bockenhauer commented on gene: SLC9A3R1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.204 | TMEM67 |
Eleanor Williams changed review comment from: Associated with several phenotypes in OMIM but ?RHYNS syndrome (#609884) is the main disease phenotype that has a skeletal component. Polydactyly may also be seen in Meckel syndrome 3 (#607361). RHYNS syndrome - 1 case: PMID: 9375913 - Di Rocco et al. (1997) - 1 case. 17.5-year-old boy with short stature, severe bone-age retardation and exhibited mild signs of skeletal dysplasia, including generalized osteopenia, epiphyseal hypoplasia, hypoplastic iliac bones with irregular acetabular margins, and thin tubular bones. He later developed nephronophthisis. Brancati et al. (2018) (PMID: 29891882) re-assessed this patient at age 38 years and reported he exhibited short stature and severe generalized osteoporosis. Skeletal survey showed moderately shortened long bones, bowed radii, short femoral neck, brachydactyly of the hands and feet with more severe involvement of middle phalanges, distal phalanx of the thumbs, and metacarpals, moderately thickened calvarium, and rotoscoliosis. Compound heterozygous variants in TMEM67 were identified, one inherited from each of his parents. PMID: 11391657 - Hedera and Gorski (2001) described 2 brothers, who had early onset retinitis pigmentosa, short stature with GH deficiency, mild facial asymmetry, and acromelic shortening of the distal extremities. They suggest this phenotype is consistent with RHYNS syndrome but no genome analysis was done. Meckel syndrome 3 - 3 out of 22 cases show polydactyly: PMID: 16415887 - Smith et al. 2006 - detected 5 different homozygous mutations in the TMEM67 in 5 consanguineous families with Meckel syndrome. The mutations were not found in over 120 ethnically matched normal control chromosomes. Polydactyly was observed in 2 out of the 5 families. PMID: 17377820 - Consugar et al. 2007 - identified 7 novel pathogenic mutations in the TMEM67 gene in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All cases were compound heterogygous. Polydactyly is reported in 1 family.; to: Associated with several phenotypes in OMIM but ?RHYNS syndrome (#609884) is the main disease phenotype that has a skeletal component. Polydactyly may also be seen in Meckel syndrome 3 (#607361). RHYNS syndrome - 1 case: PMID: 9375913 - Di Rocco et al. (1997) - 1 case. 17.5-year-old boy with short stature, severe bone-age retardation and exhibited mild signs of skeletal dysplasia, including generalized osteopenia, epiphyseal hypoplasia, hypoplastic iliac bones with irregular acetabular margins, and thin tubular bones. He later developed nephronophthisis. Brancati et al. (2018) (PMID: 29891882) re-assessed this patient at age 38 years and reported he exhibited short stature and severe generalized osteoporosis. Skeletal survey showed moderately shortened long bones, bowed radii, short femoral neck, brachydactyly of the hands and feet with more severe involvement of middle phalanges, distal phalanx of the thumbs, and metacarpals, moderately thickened calvarium, and rotoscoliosis. Compound heterozygous variants in TMEM67 were identified, one inherited from each of his parents. PMID: 11391657 - Hedera and Gorski (2001) described 2 brothers, who had early onset retinitis pigmentosa, short stature with GH deficiency, mild facial asymmetry, and acromelic shortening of the distal extremities. They suggest this phenotype is consistent with RHYNS syndrome but no genome analysis was done. Meckel syndrome 3 - 3 out of 22 cases show polydactyly: PMID: 16415887 - Smith et al. 2006 - detected 5 different homozygous mutations in the TMEM67 in 5 consanguineous families with Meckel syndrome. The mutations were not found in over 120 ethnically matched normal control chromosomes. Polydactyly was observed in 2 out of the 5 families. PMID: 17377820 - Consugar et al. 2007 - identified 7 novel pathogenic mutations in the TMEM67 gene in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All cases were compound heterogygous. Polydactyly is reported in 1 family. |
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| Adult onset neurodegenerative disorder v1.107 | Louise Daugherty Panel types changed to GMS Rare Disease | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.130 | PDE2A | Louise Daugherty changed review comment from: PMID: 29392776 Only identified in one family with infantile onset chorea predominant movement disorder, not enough evidence to rate Green unless additional evidence from labs.; to: PMID: 29392776 Only identified in one family with infantile onset chorea predominant movement disorder, not enough evidence to rate Green unless additional evidence from labs. it is currently not associated with any phenotypes in OMIM or G2P | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.130 | PDE2A | Louise Daugherty commented on gene: PDE2A: PMID: 29392776 Only identified in one family with infantile onset chorea predominant movement disorder, not enough evidence to rate Green unless additional evidence from labs. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.130 | PDE2A | Louise Daugherty Classified gene: PDE2A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.130 | PDE2A | Louise Daugherty Added comment: Comment on list classification: downgraded to Amber until evidence from GLH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.130 | PDE2A | Louise Daugherty Gene: pde2a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.129 | VAMP2 | Louise Daugherty Classified gene: VAMP2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.129 | VAMP2 | Louise Daugherty Added comment: Comment on list classification: downgraded to amber until evidence from the GLH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.129 | VAMP2 | Louise Daugherty Gene: vamp2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.128 | VAMP2 | Louise Daugherty edited their review of gene: VAMP2: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.128 | VAMP2 | Louise Daugherty edited their review of gene: VAMP2: Added comment: PMID: 30929742 : Literature reports 5 individuals, all with heterozygous de novo variants in VAMP2, it is currently not associated with any phenotypes in OMIM or G2P; Changed rating: GREEN; Changed publications: 30929742; Changed phenotypes: Cortical visual impairment, Seizures, Stereotypic behavior, Generalized hypotonia, Intellectual disability, Abnormality of movement, Global developmental delay, Generalized hypotonia, Global developmental delay, Intellectual disability, Autistic behavior, Stereotypic behavior, Seizures, Abnormality of movement, Cortical visual impairment, Autistic behavior; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cystic kidney disease v2.0 | ALG8 | Eleanor Williams edited their review of gene: ALG8: Changed rating: GREEN; Changed publications: 28375157; Changed phenotypes: Polycystic liver disease 3 with or without kidney cysts, 617874; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cystic kidney disease v2.0 | ALG8 |
Eleanor Williams changed review comment from: Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM. PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts (1, at least 3, 3-4 and 9). 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently. PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts. Will check with the Genomics England clinical team whether the level of kidney cysts seen in Besse et al is sufficient to rate this gene green on the panel. ; to: Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM. PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts (1, at least 3, 3-4 and 9). 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently. The proband with 3-4 kidney cysts has a daughter who shares the ALG8 variants and who has no liver cysts but 8 kidney cysts. PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts. |
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| Cystic kidney disease v2.0 | SEC61A1 |
Eleanor Williams changed review comment from: Associated with Hyperuricemic nephropathy, familial juvenile, 4, #617056 (AD) in OMIM. PMID: 27392076 - Bolar et al 2016 - report on two families with Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) and congenital anemia accompanied by either intrauterine growth retardation or neutropenia. The father in family B had multiple bilateral simple cysts throughout the kidney. In both families heterozygous missense variants in SEC61A1 were identified - c.553A>G (p.Thr185Ala) and c.200T>G (p.Val67Gly) -both affecting functionally important and conserved residues in SEC61. Functional studies support the renal function for this gene. PMID: 31488840- Devuyst et al 2019 - a primer that highlights the different types of ADTKD - no new cases Summary - 1 case reported with kidney cysts; to: Associated with Hyperuricemic nephropathy, familial juvenile, 4, #617056 (AD) in OMIM. PMID: 27392076 - Bolar et al 2016 - report on two families with Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) and congenital anemia accompanied by either intrauterine growth retardation or neutropenia. The father in family B had multiple bilateral simple cysts throughout the kidney. In both families heterozygous missense variants in SEC61A1 were identified - c.553A>G (p.Thr185Ala) and c.200T>G (p.Val67Gly) -both affecting functionally important and conserved residues in SEC61. Functional studies support the renal function for this gene. PMID: 31488840- Devuyst et al 2019 - a primer that highlights the different types of ADTKD - no new cases PMID: 30586318 - Groopman et al 2018 - report 1 case with a heterozygous missense variant in SEC61A1 (p.I428M). The clinical diagnosis was 'Congenital or cystic renal disease' and the genetic diagnosis 'Hyperuricemic nephropathy familial juvenile 4' (See TableS7). Summary - 2 cases reported with kidney cysts |
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| Tubulointerstitial kidney disease v1.0 | SEC61A1 | Eleanor Williams edited their review of gene: SEC61A1: Added comment: Upgrading review rating to green, the Groopman paper increases the number of cases to 3.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sarcoma cancer susceptibility v1.15 | Louise Daugherty List of related panels changed from Sarcoma;Sarcoma pertinent cancer susceptibility to Sarcoma; Sarcoma pertinent cancer susceptibility | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hydrocephalus v2.1 | Louise Daugherty List of related panels changed from Hydrocephalus; R86 to Hydrocephalus; R86 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Haematological malignancies cancer susceptibility v1.20 | Louise Daugherty List of related panels changed from Haemonc;Haematological malignancies pertinent cancer susceptibility to Haemonc; Haematological malignancies pertinent cancer susceptibility | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood solid tumours cancer susceptibility v1.6 | Louise Daugherty List of related panels changed from Childhood;Childhood solid tumours pertinent cancer susceptibility to Childhood; Childhood solid tumours pertinent cancer susceptibility | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.50 | SLC9A3R1 |
Eleanor Williams changed review comment from: Associated with Nephrolithiasis/osteoporosis, hypophosphatemic, 2 #612287 (AD) in OMIM. A previous name for SLC9A3R1 is NHERF1. Evidence for association comes from PMID: 18784102 - Karim et al 2008 - sequencing of the coding region of NHERF1 in 92 patients who presented with either renal stones or bone demineralization, together with normal serum PTH concentrations and who had no evidence of any usual causes of these disorders (e.g., hyperparathyroidism, hyperthyroidism, or an increased FGF-23 plasma concentration). These were group 1 patients. They identified three distinct missense mutations in the NHERF1 gene in four unrelated patients from group 1 (328C->G, L110V; 458G->A, R153Q; 673G->A, E225K). They also studied patients who did not have renal stones or bone demineralization (group 2) who were referred to the clinical investigation department for renal assessment before undergoing a potentially nephrotoxic treatment for psoriasis. One patient in group 2 had an NHERF1 mutation (L110V). This patient had a low TmP/GFR value.; to: Associated with Nephrolithiasis/osteoporosis, hypophosphatemic, 2 #612287 (AD) in OMIM. A previous name for SLC9A3R1 is NHERF1. Evidence for association comes from PMID: 18784102 - Karim et al 2008 - sequencing of the coding region of NHERF1 in 92 patients who presented with either renal stones or bone demineralization, together with normal serum PTH concentrations and who had no evidence of any usual causes of these disorders (e.g., hyperparathyroidism, hyperthyroidism, or an increased FGF-23 plasma concentration). These were group 1 patients. They identified three distinct missense mutations in the NHERF1 gene in four unrelated patients from group 1 (328C->G, L110V; 458G->A, R153Q; 673G->A, E225K). They also studied patients who did not have renal stones or bone demineralization (group 2) who were referred to the clinical investigation department for renal assessment before undergoing a potentially nephrotoxic treatment for psoriasis. One patient in group 2 had an NHERF1 mutation (L110V). This patient had a low TmP/GFR value. PMID: 28893421 - Daga et al 2018 - performed WES in 65 individuals from 51 families with nephrolithiasis and/or a finding of nephrocalcinosis on renal ultrasound, who manifested before the age of 25 years. They found 1 individual with a heterozygous pathogenic variant in SLC9A3R1 (c.673G>A, p.E225K). |
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| Nephrocalcinosis or nephrolithiasis v1.50 | SLC9A3R1 | Eleanor Williams commented on gene: SLC9A3R1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.407 | Ellen McDonagh Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS Rare Disease Virtual | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.406 | Ellen McDonagh List of related panels changed from Epilepsy Plus; Epilepsy plus other features; Genetic Epilepsy Syndromes; Epileptic encephalopathy; Familial Focal Epilepsies; Familial Genetic Generalised Epilepsies; Genetic Epilepsies with Febrile Seizures Plus (GEFS+); Genetic Epilepsies with Febrile Seizures Plus; Early onset or syndromic epilepsy to Epilepsy Plus; Epilepsy plus other features; Genetic Epilepsy Syndromes; Epileptic encephalopathy; Familial Focal Epilepsies; Familial Genetic Generalised Epilepsies; Genetic Epilepsies with Febrile Seizures Plus (GEFS+); Genetic Epilepsies with Febrile Seizures Plus; Early onset or syndromic epilepsy; R59 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Holoprosencephaly - NOT chromosomal v2.1 | Ellen McDonagh List of related panels changed from Rhombencephalosynapsis; Holoprosencephaly - NOT chromosomal; R85 to Rhombencephalosynapsis; Holoprosencephaly - NOT chromosomal; R85 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other rare neuromuscular disorders v1.12 | Ellen McDonagh List of related panels changed from Other rare neuromuscular disorders; R381 to Other rare neuromuscular disorders; R381 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v2.6 | Ellen McDonagh List of related panels changed from Childhood onset hereditary spastic paraplegia; Childhood onset hereditary spastic paraplegia; R61 to Childhood onset hereditary spastic paraplegia; R61 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v2.5 | Ellen McDonagh List of related panels changed from Childhood onset hereditary spastic paraplegia; R61 to Childhood onset hereditary spastic paraplegia; Childhood onset hereditary spastic paraplegia; R61 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders v4.353 | Ellen McDonagh List of related panels changed from Acutely unwell children with a likely monogenic disorder; Congenital malformation and dysmorphism syndromes - microarray and sequencing; R14; R27 to Acutely unwell children with a likely monogenic disorder; Congenital malformation and dysmorphism syndromes - microarray and sequencing; Congenital malformation and dysmorphism syndromes; R14; R27 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.393 | Ellen McDonagh List of related panels changed from Likely inborn error of metabolism - targeted testing not possible to Likely inborn error of metabolism - targeted testing not possible; Likely inborn error of metabolism; R98 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.204 | RPL13 |
Eleanor Williams gene: RPL13 was added gene: RPL13 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: RPL13 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RPL13 were set to 31630789 Phenotypes for gene: RPL13 were set to Spondyloepimetaphyseal Dysplasia with Severe Short Stature Review for gene: RPL13 was set to GREEN Added comment: PMID: 31630789 - Le Caignec et al 2019 - report one de novo missense variant (c.548G>C [p.Arg183Pro]) and three de novo splice variants in RPL13, which encodes ribosomal protein RPL13, in four unrelated individuals with a rare bone dysplasia causing severe short stature. The three splice variants (c.477þ1G>T, c.477þ1G>A, and c.477þ2 T>C) result in partial intron retention, which leads to an 18-amino acid insertion. Sources: Literature |
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| Cystic kidney disease v2.0 | SEC61A1 | Eleanor Williams reviewed gene: SEC61A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27392076; Phenotypes: Hyperuricemic nephropathy, familial juvenile, 4, 617056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cystic kidney disease v2.0 | ALG8 |
Eleanor Williams changed review comment from: Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM. PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts. 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently. PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts. Will check with the Genomics England clinical team whether the level of kidney cysts seen in Besse et al is sufficient to rate this gene green on the panel. ; to: Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM. PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts (1, at least 3, 3-4 and 9). 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently. PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts. Will check with the Genomics England clinical team whether the level of kidney cysts seen in Besse et al is sufficient to rate this gene green on the panel. |
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| Possible mitochondrial disorder - nuclear genes v1.12 | SSBP1 |
Carl Fratter changed review comment from: The publications above indicate that pathogenic variants cause disease via a dominant negative effect. 7 different variants have been reported in 9 unrelated families/individuals. Only one variant has been reported in association with biallelic (autosomal recessive) inheritance to date; i.e. the majority of reported cases are of monoallelic (autosomal dominant) inheritance.; to: The publications above indicate that pathogenic variants cause disease via a dominant negative effect. 7 different variants have been reported in 9 unrelated families/individuals. Only one variant has been reported in association with biallelic (autosomal recessive) inheritance to date; i.e. the majority of reported cases are of monoallelic (autosomal dominant) inheritance. Green rating has been proposed by the GMS Mitochondrial specialist test group on the basis of the evidence summarised here. |
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| Mitochondrial DNA maintenance disorder v1.0 | SSBP1 | Carl Fratter reviewed gene: SSBP1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 31298765, 31550240; Phenotypes: optic atrophy, optic atrophy with additional features (including retinal degeneration); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Possible mitochondrial disorder - nuclear genes v1.12 | SSBP1 | Carl Fratter reviewed gene: SSBP1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 31298765, 31550240; Phenotypes: optic atrophy, optic atrophy with additional features (including retinal degeneration); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v2.0 | Louise Daugherty promoted panel to version 2.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.138 | Louise Daugherty Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.137 | USP18 | Louise Daugherty commented on gene: USP18: Gene was flagged as requiring further clinical input from the Immunology Test Group, but no additional information was submitted to support the Green rating. In view of a lack of clear evidence the current recommendation is Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.137 | PSMB9 | Louise Daugherty commented on gene: PSMB9: Gene was flagged as requiring further clinical input from the Immunology Test Group, but no additional information was submitted to support the Green rating. In view of a lack of clear evidence the current recommendation is Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.137 | PSMB4 | Louise Daugherty commented on gene: PSMB4: Gene was flagged as requiring further clinical input from the Immunology Test Group, but no additional information was submitted to support the Green rating. In view of a lack of clear evidence the current recommendation is Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.137 | PSMA3 | Louise Daugherty commented on gene: PSMA3: Gene was flagged as requiring further clinical input from the Immunology Test Group, but no additional information was submitted to support the Green rating. In view of a lack of clear evidence the current recommendation is Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.137 | NRAS | Louise Daugherty commented on gene: NRAS: Gene was flagged as requiring further clinical input from the Immunology Test Group, but no additional information was submitted to support the Green rating. In view of a lack of clear evidence the current recommendation is Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.137 | NLRP1 | Louise Daugherty commented on gene: NLRP1: Gene was flagged as requiring further clinical input from the Immunology Test Group, but no additional information was submitted to support the Green rating. In view of a lack of clear evidence the current recommendation is Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.137 | CFB | Louise Daugherty commented on gene: CFB: Gene was flagged as requiring further clinical input from the Immunology Test Group, but no additional information was submitted to support the Green rating. In view of a lack of clear evidence the current recommendation is Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cystic kidney disease v2.0 | ALG8 |
Eleanor Williams changed review comment from: Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM. PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts. 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently. PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts.; to: Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM. PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts. 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently. PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts. Will check with the Genomics England clinical team whether the level of kidney cysts seen in Besse et al is sufficient to rate this gene green on the panel. |
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| Cytopenia - NOT Fanconi anaemia v1.0 | Louise Daugherty promoted panel to version 1.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cystic kidney disease v2.0 | ALG9 | Eleanor Williams edited their review of gene: ALG9: Changed rating: GREEN; Changed publications: 31395617, 28932688; Changed phenotypes: Gillessen-Kaesbach-Nishimura syndrome, 263210; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cystic kidney disease v2.0 | ALG9 |
Eleanor Williams changed review comment from: Associated with Gillessen-Kaesbach-Nishimura syndrome, 263210 (AR) in OMIM in which Polycystic kidneys is listed as a clinical feature. PMID: 31395617 - Besse et al 2019 - report 2 patients in a clinically defined cohort with genetically unresolved polycystic liver and kidney disease that had rare heterozygous loss-of-function variants in ALG9. Then using a novel ‘genotype-first’ approach to find ALG9 mutation carriers from a large cohort of exome-sequenced individuals, they found that 7/8 (88%) of ALG9 mutation carriers over age 50 had a least 4 kidney cysts (abstract only accessed). PMID: 28932688 - Davis et al 2017 - report the case of a proband with ALG9-CDG who has a milder phenotype. This female child was born to non-consanguineous parents of Scottish decent. Prenatally, dysmorphic features, numerous renal cysts and minor cardiac malformations were detected. Post-natally, dysmorphic features included shallow orbits, micrognathia, hypoplastic nipples, talipes equinovarus, lipodystrophy and cutis marmorata. She developed failure to thrive and seizures. A homozygous mutation in ALG9, c.860A > G (p.Tyr287Cys) was identified. Both parents were found to carry one copy of the mutation. In a table of phenotypic features from the 11 known patients with ALG9-CDG (including the one here), 3 other patients are reported with polycystic kidneys and homozygous ALG variants.; to: Associated with Gillessen-Kaesbach-Nishimura syndrome, 263210 (AR) in OMIM in which Polycystic kidneys is listed as a clinical feature. PMID: 31395617 - Besse et al 2019 - report 2 patients in a clinically defined cohort with genetically unresolved polycystic liver and kidney disease that had rare heterozygous loss-of-function variants in ALG9. Then using a novel ‘genotype-first’ approach to find ALG9 mutation carriers from a large cohort of exome-sequenced individuals, they found that 7/8 (88%) of ALG9 mutation carriers over age 50 had a least 4 kidney cysts (abstract only accessed). PMID: 28932688 - Davis et al 2017 - report the case of a proband with ALG9-CDG who has a milder phenotype. This female child was born to non-consanguineous parents of Scottish decent. Prenatally, dysmorphic features, numerous renal cysts and minor cardiac malformations were detected. Post-natally, dysmorphic features included shallow orbits, micrognathia, hypoplastic nipples, talipes equinovarus, lipodystrophy and cutis marmorata. She developed failure to thrive and seizures. A homozygous mutation in ALG9, c.860A > G (p.Tyr287Cys) was identified. Both parents were found to carry one copy of the mutation. In a table of phenotypic features from the 11 known patients with ALG9-CDG (including the one here), 3 other patients are reported with polycystic kidneys and homozygous ALG variants. |
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| Cystic kidney disease v2.0 | ALG9 | Eleanor Williams commented on gene: ALG9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.137 | Louise Daugherty Panel types changed to GMS Rare Disease; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.21 | CNBP_CCTG | Louise Daugherty commented on STR: CNBP_CCTG: As discussed in PanelApp team meeting a new tag "NGS Not Validated". This STR currently has not be validated within the Genomics England pipeline. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Distal myopathies v1.11 | CNBP_CCTG | Louise Daugherty commented on STR: CNBP_CCTG | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.26 | CNBP_CCTG | Louise Daugherty commented on STR: CNBP_CCTG: As discussed in PanelApp team meeting a new tag "NGS Not Validated". This STR currently has not be validated within the Genomics England pipeline. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.26 | CNBP_CCTG | Louise Daugherty Tag NGS Not Validated tag was added to STR: CNBP_CCTG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Distal myopathies v1.11 | CNBP_CCTG | Louise Daugherty Tag NGS Not Validated tag was added to STR: CNBP_CCTG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.21 | CNBP_CCTG | Louise Daugherty Tag NGS Not Validated tag was added to STR: CNBP_CCTG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cystic kidney disease v2.0 | ALG8 | Eleanor Williams commented on gene: ALG8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disorders v2.2 | ABCB7 | Ivone Leong Added comment: Comment on mode of inheritance: Change MOI from "X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)" to "X-LINKED: hemizygous mutation in males, biallelic mutations in females" to reflect the MOI that is given to this gene on the "Possible mitochondrial disorder - nuclear genes" (code: 539, v1.12). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disorders v2.2 | ABCB7 | Ivone Leong Mode of inheritance for gene: ABCB7 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.137 | CSF2RA | Louise Daugherty Added comment: Comment on mode of inheritance: Changed MOI due to MOI checks carried out by PanelApp team. This gene is on the pseudoautosomal region of chromosome X which is shared with chromoseome Y, so MOI affected cases are biallelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.137 | CSF2RA | Louise Daugherty Mode of inheritance for gene: CSF2RA was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v2.4 | RNASEH2B | Louise Daugherty Publications for gene: RNASEH2B were set to 30223285; :25243380; 29691679; 28762473 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v2.3 | RNASEH2B | Louise Daugherty Phenotypes for gene: RNASEH2B were changed from hereditary spastic paraparesis to Aicardi-Goutieres syndrome 2, 610181; spastic paraparesis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.148 | NUP107 | Rebecca Foulger changed review comment from: Original DDG2P rating: confirmed. ; to: Original DDG2P rating for EARLY-CHILDHOOD-ONSET STEROID-RESISTANT NEPHROTIC SYNDROME: confirmed. DDG2P Mutation consequence: loss of function. DDG2P Allelic requirement: biallelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v2.2 | RNASEH2B | Louise Daugherty Classified gene: RNASEH2B as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v2.2 | RNASEH2B | Louise Daugherty Added comment: Comment on list classification: New Green rated gene added by reviewer after panel sign off to V1.0- to be reviewed at next panel update with the Neurology Test Group for GMS. The 100,000 Genomes Project has identified one case and recent publications have reported RNASEH2B variants in homozygous status in patients with spastic paraplegia. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v2.2 | RNASEH2B | Louise Daugherty Gene: rnaseh2b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v2.1 | RNASEH2B | Louise Daugherty Publications for gene: RNASEH2B were set to PMID:30223285, PMID:25243380, PMID:29691679 and PMID:28762473 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v2.0 | RNASEH2B |
Zerin Hyder gene: RNASEH2B was added gene: RNASEH2B was added to Hereditary spastic paraplegia - childhood onset. Sources: Other Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2B were set to PMID:30223285, PMID:25243380, PMID:29691679 and PMID:28762473 Phenotypes for gene: RNASEH2B were set to hereditary spastic paraparesis Penetrance for gene: RNASEH2B were set to unknown Mode of pathogenicity for gene: RNASEH2B was set to Other Review for gene: RNASEH2B was set to GREEN Added comment: Above publications report the association of pure, childhood-onset spastic paraparesis in association with missense recessive variants in RNASEH2B. Sources: Other |
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| Adult onset hereditary spastic paraplegia v1.2 | Louise Daugherty removed gene:RNASEH2B from the panel | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.95 | WDR37 |
Zerin Hyder gene: WDR37 was added gene: WDR37 was added to Structural eye disease. Sources: Other Mode of inheritance for gene: WDR37 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WDR37 were set to PMID:31327510, PMID:31327508 Phenotypes for gene: WDR37 were set to corneal opacity; Peters anomaly; coloboma; microcornea Penetrance for gene: WDR37 were set to unknown Review for gene: WDR37 was set to AMBER Added comment: Features of WDR37 syndrome include the following: ocular anomalies such as corneal opacity/Peters anomaly, coloboma, and microcornea; dysmorphic facial features; significant neurological impairment with structural brain defects and seizures; poor feeding; poor post-natal growth; variable skeletal, cardiac, and genitourinary defects. The probands in one paper exhibited shared phenotypes of epilepsy, colobomas, facial dysmorphology reminiscent of CHARGE syndrome, developmental delay and intellectual disability, and cerebellar hypoplasia Sources: Other |
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| Hereditary spastic paraplegia v1.210 | RNASEH2B | Louise Daugherty Classified gene: RNASEH2B as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary spastic paraplegia v1.210 | RNASEH2B | Louise Daugherty Added comment: Comment on list classification: New gene added. The 100,000 Genomes Project has identified one case and recent publications have reported RNASEH2B variants in homozygous status in patients with spastic paraplegia. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary spastic paraplegia v1.210 | RNASEH2B | Louise Daugherty Gene: rnaseh2b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary spastic paraplegia v1.209 | RNASEH2B | Louise Daugherty Phenotypes for gene: RNASEH2B were changed from spastic paraparesis to Aicardi-Goutieres syndrome 2, 610181; spastic paraparesis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary spastic paraplegia v1.208 | RNASEH2B | Louise Daugherty Publications for gene: RNASEH2B were set to PMID:30223285, PMID:25243380, PMID:29691679 and PMID:28762473 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset hereditary spastic paraplegia v1.1 | RNASEH2B |
Zerin Hyder gene: RNASEH2B was added gene: RNASEH2B was added to Hereditary spastic paraplegia - adult onset. Sources: Other Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2B were set to PMID:30223285, PMID:25243380, PMID:29691679 and PMID:28762473 Phenotypes for gene: RNASEH2B were set to hereditary spastic paraparesis Mode of pathogenicity for gene: RNASEH2B was set to Other Review for gene: RNASEH2B was set to GREEN Added comment: Above publications report association of pure, childhood-onset spastic paraparesis in association with missense recessive variants in RNASEH2B. Sources: Other |
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| Hereditary spastic paraplegia v1.207 | RNASEH2B |
Zerin Hyder gene: RNASEH2B was added gene: RNASEH2B was added to Hereditary spastic paraplegia. Sources: Other Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2B were set to PMID:30223285, PMID:25243380, PMID:29691679 and PMID:28762473 Phenotypes for gene: RNASEH2B were set to spastic paraparesis Penetrance for gene: RNASEH2B were set to unknown Mode of pathogenicity for gene: RNASEH2B was set to Other Review for gene: RNASEH2B was set to GREEN Added comment: Abovepublications report association of pure, childhood-onset spastic paraparesis in association with missense recessive variants in RNASEH2B. Sources: Other |
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| Polycystic liver disease v1.0 | Ivone Leong promoted panel to version 1.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Polycystic liver disease v0.9 | Ivone Leong Panel types changed to GMS Rare Disease; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy v1.337 | WARS | Louise Daugherty Classified gene: WARS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy v1.337 | WARS | Louise Daugherty Added comment: Comment on list classification: new gene added from the GLH, this gene was rated as Green due to cases in the 100,000 Genomes Project in addition to the published cases | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy v1.337 | WARS | Louise Daugherty Gene: wars has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy v1.336 | WARS | Louise Daugherty Publications for gene: WARS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.346 | BICD2 | Suzanne Drury reviewed gene: BICD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27751653, 29274205, 28635954; Phenotypes: HP:0002804, HP:0001059; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Respiratory ciliopathies including non-CF bronchiectasis v1.2 | FOXJ1 | Louise Daugherty Publications for gene: FOXJ1 were set to PMID: 31630787 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Respiratory ciliopathies including non-CF bronchiectasis v1.1 | FOXJ1 | Louise Daugherty Classified gene: FOXJ1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Respiratory ciliopathies including non-CF bronchiectasis v1.1 | FOXJ1 | Louise Daugherty Added comment: Comment on list classification: New gene added by external reviewer after panel sign off to V1.0- to be reviewed at next panel update with the respiratory Test Group for GMS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Respiratory ciliopathies including non-CF bronchiectasis v1.1 | FOXJ1 | Louise Daugherty Gene: foxj1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.162 | TCTN3 | Eleanor Williams Classified gene: TCTN3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.162 | TCTN3 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.162 | TCTN3 | Eleanor Williams Gene: tctn3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.161 | TCTN3 | Eleanor Williams Mode of inheritance for gene: TCTN3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.160 | TCTN3 | Eleanor Williams Publications for gene: TCTN3 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.159 | TCTN3 | Eleanor Williams Phenotypes for gene: TCTN3 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome 18 614815 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.158 | TMEM231 | Eleanor Williams Classified gene: TMEM231 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.158 | TMEM231 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.158 | TMEM231 | Eleanor Williams Gene: tmem231 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.157 | TMEM138 | Eleanor Williams Classified gene: TMEM138 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.157 | TMEM138 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.157 | TMEM138 | Eleanor Williams Gene: tmem138 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.156 | TMEM138 | Eleanor Williams Mode of inheritance for gene: TMEM138 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.155 | TMEM138 | Eleanor Williams Publications for gene: TMEM138 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.154 | TMEM138 | Eleanor Williams Phenotypes for gene: TMEM138 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome 16 614465 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.153 | TMEM216 | Eleanor Williams Classified gene: TMEM216 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.153 | TMEM216 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.153 | TMEM216 | Eleanor Williams Gene: tmem216 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.152 | TMEM216 | Eleanor Williams Mode of inheritance for gene: TMEM216 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.151 | TMEM216 | Eleanor Williams Publications for gene: TMEM216 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.150 | TMEM216 | Eleanor Williams Phenotypes for gene: TMEM216 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome 2 608091; Meckel syndrome 2 603194 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.149 | TMEM231 | Eleanor Williams Mode of inheritance for gene: TMEM231 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.148 | TMEM231 | Eleanor Williams Publications for gene: TMEM231 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.147 | TMEM231 | Eleanor Williams Phenotypes for gene: TMEM231 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome 20 614970; Meckel syndrome 11 615397 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.146 | TMEM237 | Eleanor Williams Classified gene: TMEM237 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.146 | TMEM237 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.146 | TMEM237 | Eleanor Williams Gene: tmem237 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.145 | TMEM237 | Eleanor Williams Mode of inheritance for gene: TMEM237 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.144 | TMEM237 | Eleanor Williams Publications for gene: TMEM237 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.143 | TMEM237 | Eleanor Williams Phenotypes for gene: TMEM237 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome 14 614424 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.142 | TTC8 | Eleanor Williams Classified gene: TTC8 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.142 | TTC8 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.142 | TTC8 | Eleanor Williams Gene: ttc8 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.141 | TTC8 | Eleanor Williams Publications for gene: TTC8 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.140 | TTC8 | Eleanor Williams Phenotypes for gene: TTC8 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Bardet-Biedl syndrome 8 615985 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.139 | TTC8 | Eleanor Williams Mode of inheritance for gene: TTC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.138 | WDPCP | Eleanor Williams Classified gene: WDPCP as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.138 | WDPCP | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.138 | WDPCP | Eleanor Williams Gene: wdpcp has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.137 | WDPCP | Eleanor Williams Mode of inheritance for gene: WDPCP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.136 | WDPCP | Eleanor Williams Phenotypes for gene: WDPCP were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; ?Bardet-Biedl syndrome 15 615992 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.135 | TCTN1 | Eleanor Williams Classified gene: TCTN1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.135 | TCTN1 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.135 | TCTN1 | Eleanor Williams Gene: tctn1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.134 | TCTN1 | Eleanor Williams Mode of inheritance for gene: TCTN1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.133 | TCTN1 | Eleanor Williams Phenotypes for gene: TCTN1 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome 13 614173 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.132 | SDCCAG8 | Eleanor Williams Classified gene: SDCCAG8 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.132 | SDCCAG8 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.132 | SDCCAG8 | Eleanor Williams Gene: sdccag8 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.131 | SDCCAG8 | Eleanor Williams Publications for gene: SDCCAG8 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.130 | SDCCAG8 | Eleanor Williams Phenotypes for gene: SDCCAG8 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Bardet-Biedl syndrome 16 615993; Senior-Loken syndrome 7 613615 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.129 | SDCCAG8 | Eleanor Williams Mode of inheritance for gene: SDCCAG8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.128 | PMM2 | Eleanor Williams Classified gene: PMM2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.128 | PMM2 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.128 | PMM2 | Eleanor Williams Gene: pmm2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.127 | PMM2 | Eleanor Williams Phenotypes for gene: PMM2 were changed from to Congenital disorder of glycosylation, type Ia 212065 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.126 | PMM2 | Eleanor Williams Added comment: Comment on publications: Publication from the renal ciliopathies panel | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.126 | PMM2 | Eleanor Williams Publications for gene: PMM2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.125 | PMM2 | Eleanor Williams Mode of inheritance for gene: PMM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.124 | NEK8 | Eleanor Williams Classified gene: NEK8 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.124 | NEK8 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.124 | NEK8 | Eleanor Williams Gene: nek8 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.123 | MKS1 | Eleanor Williams Classified gene: MKS1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.123 | MKS1 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.123 | MKS1 | Eleanor Williams Gene: mks1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.122 | MKS1 | Eleanor Williams Mode of inheritance for gene: MKS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.121 | MKS1 | Eleanor Williams Publications for gene: MKS1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.120 | MKS1 | Eleanor Williams Phenotypes for gene: MKS1 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Bardet-Biedl syndrome 13 615990; Meckel syndrome 1 249000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.119 | KIF7 | Eleanor Williams Classified gene: KIF7 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.119 | KIF7 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.119 | KIF7 | Eleanor Williams Gene: kif7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.118 | KIF7 | Eleanor Williams Added comment: Comment on mode of inheritance: Acrocallosal syndrome/Joubert syndrome 12 are listed as AR in OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.118 | KIF7 | Eleanor Williams Mode of inheritance for gene: KIF7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.117 | KIF7 | Eleanor Williams Phenotypes for gene: KIF7 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Acrocallosal syndrome 200990; Joubert syndrome 12 200990 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.116 | INPP5E | Eleanor Williams Classified gene: INPP5E as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.116 | INPP5E | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.116 | INPP5E | Eleanor Williams Gene: inpp5e has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.115 | INPP5E | Eleanor Williams Mode of inheritance for gene: INPP5E was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.114 | INPP5E | Eleanor Williams Phenotypes for gene: INPP5E were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome 1 213300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.113 | CEP41 | Eleanor Williams Classified gene: CEP41 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.113 | CEP41 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.113 | CEP41 | Eleanor Williams Gene: cep41 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.112 | CEP41 | Eleanor Williams Mode of inheritance for gene: CEP41 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.111 | CEP41 | Eleanor Williams Phenotypes for gene: CEP41 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome 15 614464 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.110 | CEP290 | Eleanor Williams Classified gene: CEP290 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.110 | CEP290 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.110 | CEP290 | Eleanor Williams Gene: cep290 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.109 | CEP290 | Eleanor Williams Publications for gene: CEP290 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.108 | CEP290 | Eleanor Williams Phenotypes for gene: CEP290 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome 5 610188lLeber congenital amaurosis 10 611755 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.107 | CC2D2A | Eleanor Williams Classified gene: CC2D2A as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.107 | CC2D2A | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.107 | CC2D2A | Eleanor Williams Gene: cc2d2a has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.106 | CC2D2A | Eleanor Williams Mode of inheritance for gene: CC2D2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.105 | CC2D2A | Eleanor Williams Publications for gene: CC2D2A were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.104 | CC2D2A | Eleanor Williams Phenotypes for gene: CC2D2A were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome 9 612285; Meckel syndrome 6 612284 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.103 | C5orf42 | Eleanor Williams Classified gene: C5orf42 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.103 | C5orf42 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.103 | C5orf42 | Eleanor Williams Gene: c5orf42 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.102 | C5orf42 | Eleanor Williams Mode of inheritance for gene: C5orf42 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.101 | C5orf42 | Eleanor Williams Publications for gene: C5orf42 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.100 | C5orf42 | Eleanor Williams Phenotypes for gene: C5orf42 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome 17 614615 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.99 | BBS9 | Eleanor Williams Classified gene: BBS9 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.99 | BBS9 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.99 | BBS9 | Eleanor Williams Gene: bbs9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.98 | BBS9 | Eleanor Williams Mode of inheritance for gene: BBS9 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.97 | BBS9 | Eleanor Williams Publications for gene: BBS9 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.96 | BBS9 | Eleanor Williams Phenotypes for gene: BBS9 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Bardet-Biedl syndrome 9 615986 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.95 | BBS5 | Eleanor Williams Classified gene: BBS5 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.95 | BBS5 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.95 | BBS5 | Eleanor Williams Gene: bbs5 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.94 | BBS5 | Eleanor Williams Mode of inheritance for gene: BBS5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.93 | BBS5 | Eleanor Williams Publications for gene: BBS5 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.92 | BBS5 | Eleanor Williams Phenotypes for gene: BBS5 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Bardet-Biedl syndrome 5 615983 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.91 | BBS4 | Eleanor Williams Classified gene: BBS4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.91 | BBS4 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.91 | BBS4 | Eleanor Williams Gene: bbs4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.90 | BBS4 | Eleanor Williams Mode of inheritance for gene: BBS4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.89 | BBS4 | Eleanor Williams Publications for gene: BBS4 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.88 | BBS4 | Eleanor Williams Phenotypes for gene: BBS4 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Bardet-Biedl syndrome 4 615982 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.87 | BBS2 | Eleanor Williams Classified gene: BBS2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.87 | BBS2 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.87 | BBS2 | Eleanor Williams Gene: bbs2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.86 | BBS2 | Eleanor Williams Mode of inheritance for gene: BBS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.85 | BBS2 | Eleanor Williams Publications for gene: BBS2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.84 | BBS2 | Eleanor Williams Phenotypes for gene: BBS2 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Bardet-Biedl syndrome 2 615981 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.83 | BBS12 | Eleanor Williams Classified gene: BBS12 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.83 | BBS12 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.83 | BBS12 | Eleanor Williams Gene: bbs12 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.82 | BBS12 | Eleanor Williams Mode of inheritance for gene: BBS12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.81 | BBS12 | Eleanor Williams Publications for gene: BBS12 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.80 | BBS12 | Eleanor Williams Phenotypes for gene: BBS12 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Bardet-Biedl syndrome 12 615989 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.79 | BBS10 | Eleanor Williams Classified gene: BBS10 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.79 | BBS10 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.79 | BBS10 | Eleanor Williams Gene: bbs10 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.78 | BBS10 | Eleanor Williams Phenotypes for gene: BBS10 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Bardet-Biedl syndrome 10 615987 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.77 | BBS10 | Eleanor Williams Publications for gene: BBS10 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.76 | BBS10 | Eleanor Williams Mode of inheritance for gene: BBS10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.75 | BBS1 | Eleanor Williams Classified gene: BBS1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.75 | BBS1 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.75 | BBS1 | Eleanor Williams Gene: bbs1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.74 | BBS1 | Eleanor Williams Phenotypes for gene: BBS1 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Bardet-Biedl syndrome type 1 209900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.73 | BBS1 | Eleanor Williams Publications for gene: BBS1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.72 | BBS1 | Eleanor Williams Mode of inheritance for gene: BBS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.71 | ARL6 | Eleanor Williams Classified gene: ARL6 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.71 | ARL6 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.71 | ARL6 | Eleanor Williams Gene: arl6 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.70 | ARL6 | Eleanor Williams Mode of inheritance for gene: ARL6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.69 | ARL6 | Eleanor Williams Publications for gene: ARL6 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.68 | ARL6 | Eleanor Williams Phenotypes for gene: ARL6 were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Bardel-Biedl syndrome type 3 600151 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.67 | ARL13B | Eleanor Williams Classified gene: ARL13B as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.67 | ARL13B | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.67 | ARL13B | Eleanor Williams Gene: arl13b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.66 | ARL13B | Eleanor Williams Phenotypes for gene: ARL13B were changed from Ciliopathy genes associated with cystic kidney disease; Joubert syndrome type 8 to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome type 8 612291 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.65 | ARL13B | Eleanor Williams Phenotypes for gene: ARL13B were changed from Ciliopathy genes associated with cystic kidney disease to Ciliopathy genes associated with cystic kidney disease; Joubert syndrome type 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.64 | ARL13B | Eleanor Williams Publications for gene: ARL13B were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.63 | ARL13B | Eleanor Williams Mode of inheritance for gene: ARL13B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.62 | ALMS1 | Eleanor Williams Classified gene: ALMS1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.62 | ALMS1 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.62 | ALMS1 | Eleanor Williams Gene: alms1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.61 | ALMS1 | Eleanor Williams Mode of inheritance for gene: ALMS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.60 | ALMS1 | Eleanor Williams Publications for gene: ALMS1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.59 | ALMS1 | Eleanor Williams Phenotypes for gene: ALMS1 were changed from to Alstrom Syndrome; Bardet-Biedl Syndrome; 203800; Alstrom syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.58 | AHI1 | Eleanor Williams Publications for gene: AHI1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.57 | AHI1 | Eleanor Williams Classified gene: AHI1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.57 | AHI1 | Eleanor Williams Added comment: Comment on list classification: Promoting to green as green on the renal ciliopathies panel https://panelapp.genomicsengland.co.uk/panels/725/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.57 | AHI1 | Eleanor Williams Gene: ahi1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1098 | CNOT2 |
Konstantinos Varvagiannis gene: CNOT2 was added gene: CNOT2 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: CNOT2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CNOT2 were set to 31512373; 31145527; 28135719; 28159701; 30768759; 21505450; 18076123; 22247066 Phenotypes for gene: CNOT2 were set to Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies, MIM 618608 Penetrance for gene: CNOT2 were set to unknown Review for gene: CNOT2 was set to GREEN gene: CNOT2 was marked as current diagnostic Added comment: Heterozygous pathogenic CNOT2 variants cause Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies (MIM 618608 - recently added disorder in OMIM). Larger 12q15 deletions, spanning CNOT2 have been reported in patients with similar phenotype. Relevant individuals - most discussed below - include 2 patients with truncating de novo mutation, 1 with de novo intragenic deletion, few with small deletions spanning also 2-3 additional proximal genes and others with larger 12q15 deletions encompassing CNOT2 and several other genes. Overall the phenotype - summarized by Uehara et al. (Ref1 - below) - seems to consist of language delay, mild motor delay (in most), some suggestive facial features (upslanted palpebral fissures, anteverted nares, thin upper lip and micrognathia). Nasal speech has also been reported in some individuals. As commented by Uehara et al. (Ref1), CNOT2 (CCR4-NOT transcription complex subunit 2) is a member of the carbon catabolite repressor 4 complex (CCR4-NOT), the latter having an important role in deadenylation of mRNA and global mRNA expression. Disruption of the complex - which can be caused by loss of one of its components - results in various human disorders incl. neural diseases. siRNA CNOT2 depletion has been shown to induce CCR4-NOT disruption (cited PMIDs: 16284618, 29438013, 31006510, 21299754). The type of variants (truncating, intragenic deletion, larger deletions) and the highly overlapping phenotypes in the respective patients suggest happloinsufficiency as the underlying mechanism. CNOT2 has also a pLI of 1 in gnomAD (o/e =0.06) and a %HI in Decipher of 4.39. The gene appears to have relevant expression (https://www.proteinatlas.org/ENSG00000111596-CNOT2/tissue). Animal models have not been discussed (or phenotypes possibly not sufficiently studied - MGI for Cnot2 : http://www.informatics.jax.org/marker/MGI:1919318). CNOT2 is not associated with any phenotype in G2P. It is listed among the ID candidate genes in SysID. This gene is included in gene panels for ID offered by some diagnostic laboratories (incl. Radboudumc). Overall CNOT2 could be considered for inclusion in the ID panel with amber (DD although outcome is not known, presumed dysfunction of the CCR4-NOT complex, variant studies or animal models not available) or green rating (sufficient cases and variants, consistent phenotype). ----- Individuals with CNOT2-only disruption: [1] PMID: 31512373 (Uehara et al., 2019) - A 6 y.o. male investigated for hypotonia, feeding problems, DD (speech and motor), macrocephaly (+3 SD) and some possibly suggestive facial/other features was found to harbor a de novo stopgain variant (NM_001199302.1: c.946A>T, p.Lys316Ter) after trio exome sequencing. The variant and its de novo occurrence were confirmed by Sanger sequencing. NMD was the predicted effect (variant in ex11 of 21 / effect not further studied). Previous metabolic work-up and chromosomal testing had not revealed an alternative diagnosis. [2] PMID: 31145527 (Alesi et al. 2019) - A 13 y.o. boy with hypotonia, failure to thrive, DD and following a specific schooling program for children with learning difficulties is reported. The authors comment on the facial phenotype (incl. upslanted p-f, anteverted nares, etc). Other features included valvular/supravalvular pulm. stenosis, mid aortic insufficiency, renal anomalies/failure, skeletal anomalies. Speech was nasal. CMA revealed an 85-kb 12q15 deletion spanning only CNOT2 (exons 3-15). Real-time PCR in proband and parents confirmed the variant and its de novo occurrence. [3] PMID: 28135719 (DDD study, 2017) - An individual with developmental disorder and a de novo (validated) frameshift variant was identified [DDD4K.00807 - NM_014515.5:c.1158del / p.(L387Sfs*3)]. Phenotype in Decipher incl. abnormality of head/neck, nervous, skeletal system and growth. [https://decipher.sanger.ac.uk/ddd/research-variant/16b4f7866652f08e25a194f65535b4c5#overview]. Individuals with disruption of additional proximal genes due to CNVs: [4] PMID: 28159701 (Alesi et al. 2017) - The authors report on a 29 y.o. individual with history of DD, learning difficulties, ID (WAIS-R IQ of 48 at the age of 17 y), some dysmorphic facial features. Additional features incl. recurrent infections, nasal voice as well as skeletal anomalies. CMA revealed a 742 kb microdeletion spanning CNOT2, KCNMB4 and PTPRB. Real-time PCR confirmed deletion and it's de novo occurrence in the proband. [5] PMID: 30768759 (Uehara et al. 2019) - A female investigated among others for global DD (walking/1st words at 24m), mild ID, submucosal cleft palate with some distinctive facial features (upslanted p-f, micrognathia, etc) was found to harbor a 1.32-Mb deletion of 12q15 encompassing CNOT2 and 14 other genes. Given the phenotypic resemblance to patients with 12q15 deletions, the previously defined smallest region of overlap (ref 4,6), the LoF SNV in Decipher the authors suggested that CNOT2 is the critical gene for the phenotype of 12q15 deletion syndrome. Larger deletions defining the smallest region of overlap [6] PMID: 21505450 (Vergult et al. 2011) - 3 patients with de novo microdeletions of ~ 2.5 Mb in size with a 1.34 MB common region of overlap are reported. Learning diability, DD, nasal speech and hypothyroidism were among the common features. [7] PMID: 18076123 (Schluth et al. 2008) - A girl with large (~10 Mb) de novo deletion of 12q15 - q21.2 identified by BAC array was described. The phenotype consisted of hypotonia, DD, moderate ID, growth delay and facial dysmorphic features. [8] PMID: 22247066 (Lopez et al. 2012) - A patient with ID and features of Floating-Harbor syndrome was found to harbor a 4.7 Mb de novo 12q15-q21.1 deletion spanning CNOT2 and 18 additional genes. [..] Sources: Literature, Radboud University Medical Center, Nijmegen |
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| Intellectual disability v2.1098 | TMX2 |
Konstantinos Varvagiannis gene: TMX2 was added gene: TMX2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: TMX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMX2 were set to 31586943; 31270415 Phenotypes for gene: TMX2 were set to Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormal cortical gyration Penetrance for gene: TMX2 were set to Complete Review for gene: TMX2 was set to AMBER Added comment: PMID: 31586943 - Ghosh et al. 2019 - reported on 8 individuals from 4 consanguineous families from the Middle East and Central Asia, all with a phenotype of DD/ID, seizures and microcephaly with lissencephaly (microlissencephaly is the term applying to the combination of two) upon brain MRI. All patients were investigated by exome sequencing and the variant localized within a region of ROH which was common to all 4 families. All were homozygous for a TMX2 missense variant (NM_001144012.2:c.500G>A or p.Arg167Gln / NM_015959.4:c.614G>A p.Arg205Gln or hg38 - Chr11:g.57739039G>A). The variant was considered to be the best candidate, upon review of all other homozygous ones. Sanger sequencing confirmed homozygosity for the variant in affected subjects, with additional compatible segregation studies including parents in all families as well as unaffected sibs (in two families). Despite presence of the same mutation in all, several proximal to this variant SNPs did not appear to be shared among the families studied, thus suggesting that the variant had arisen within different haplotype blocks. The authors comment that the variant was not previously identified in public databases. (The variant seems to correspond to rs370455806, present in 10 htz individuals in gnomAD, as well as in the GME database [GME Genotype Count 992:0:1 (hmz?) | Allele Count: 2,1984] . GME includes primarily - although not necessarily - healthy individuals). This SNV affecting the last nucleotide of an exon of several transcripts (correct ref. is NM_001144012.2 as appears in the supplement / using NM_001347898.1 as in the fig./text the variant would lie within an intron), an eventual splicing effect was studied. mRNA transcript levels were assessed following RT-PCR using different sets of primers. There was no evidence of novel splice isoforms but mRNA levels were reduced compared to controls (15-50% in affected individuals, to a lesser level in carriers). This led to the hypothesis that NMD of an aberrantly spliced mRNA might apply, although this was not proven. TMX2 encodes a protein disulfide isomerase (PDI). PDIs are transmembrane ER proteins which have a critical role in protein folding (PMID cited: 12670024). There were no relevant studies carried out in the article. As for animal models, the authors comment that mice homozygous for null mutations display preweaning lethality with complete penetrance.(http://www.informatics.jax.org/diseasePortal/popup?isPhenotype=true&markerID=MGI:1914208&header=mortality/aging). ------- Previously, Schot el al. (ESHG Conference 2018 Oral Presentation - Mutations in the thioredoxin related gene TMX2 cause primary microcephaly, polymicrogyria and severe neurodegeneration with impaired mitochondrial energy metabolism - available in PMID: 31270415 / https://www.nature.com/articles/s41431-019-0407-4 ) reported on 7 individuals from 5 unrelated families with biallelic TMX2 mutations. A newborn with microcephaly, polymicrogyria who died of refractory epilepsy, was compound heterozygous for 2 TMX2 variants. 6 additional individuals (from 4 unrelated families) with similar phenotype were found to harbor biallelic TMX2 mutations. It was commented that TMX2 is enriched in mitochondria-associated membrane of the ER with a role in ER stress protection and regulation of neuronal apoptosis. In line with this, fibroblasts from 2 unrelated patients showed secondary OXPHOS deficiency and increased glycolytic activity (the latter possibly as a compensatory mechanism). ------- There is no associated phenotype in OMIM/G2P/SysID. ------- Overall this gene could be considered for inclusion in the ID/epilepsy panel probably with amber (/red) rating pending further evidence. Sources: Literature |
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| Intellectual disability v2.1098 | KCNT2 |
Konstantinos Varvagiannis gene: KCNT2 was added gene: KCNT2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: KCNT2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KCNT2 were set to 29069600; 29740868 Phenotypes for gene: KCNT2 were set to ?Epileptic encephalopathy, early infantile 57, MIM 617771 Penetrance for gene: KCNT2 were set to unknown Review for gene: KCNT2 was set to GREEN Added comment: Heterozygous pathogenic KCNT2 variants cause ?Epileptic encephalopathy, early infantile, 57 (MIM 617771). At least 3 unrelated affected individuals have been reported : - PMID: 29069600 - Gururaj et al. 2017 : a male child with EOEE (hypotonia, profound DD and intractable infantile seizures) due to a de novo KCNT2 missense variant (NM_001287819.1:c.720T>A or p.Phe240Leu) identified by exome sequencing. - PMID: 29740868 - Ambrosino et al. 2018 : A girl with phenotype corresponding to West syndrome later evolving to Lennox-Gastaut syndrome. At the age of 9 years the girl displayed severe ID. Trio exome sequencing revealed a de novo missense KCNT2 variant (NM_001287820.2:c.569G>A or p.Arg190His). A 14 y.o. female recruited through the DDD study with phenotype corresponding to epilepsy of infancy with migrating focal seizures. The girl had poor language development and severe learning disability. Infective and metabolic causes were initially ruled out. Trio exome sequencing revealed a de novo missense SNV (c.569G>C or Arg190Pro). Overall KCNT2 has been commented to contribute to a phenotypic spectrum similar and overlapping to that of KCNT1 (Ambrosino et al.). [KCNT1 is rated green in both epilepsy and ID panels]. KCNT2 was recently included in the epilepsy panel as green (functional studies summarized in the respective reviews). The gene was also recently added to G2P, associated with 'Developmental and infantile epileptic encephalopathy'. It is not commonly included in gene panels for ID offered by diagnostic laboratories. As a result, KCNT2 could be considered for inclusion in the ID panel with green (or amber) rating. Sources: Literature |
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| Early onset or syndromic epilepsy v1.405 | NSF |
Konstantinos Varvagiannis gene: NSF was added gene: NSF was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: NSF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NSF were set to 31675180 Phenotypes for gene: NSF were set to Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability Penetrance for gene: NSF were set to unknown Review for gene: NSF was set to AMBER Added comment: Suzuki et al. (2019 - PMID: 31675180) report on 2 unrelated individuals with de novo missense NSF variants. Overall the phenotype corresponded to an early infantile epileptic encephalopathy. The first patient developed vomiting and tonic seizures immediately after birth, with burst-suppression pattern upon EEG. Trio exome sequencing, followed by Sanger sequencing of proband and parents, revealed a de novo missense variant (NM_006178.3:c.1375G>A / p.Ala459Thr), absent from public databases and predicted in silico to be deleterious (CADD score of 30). The girl died 36 days after birth due to respiratory failure. Another subject, having necessitated mechanical ventilation due to absence of spontaneous respiration after birth, developed myoclonic seizures. EEG showed a burst-suppression pattern. At the age of 3, she was noted to have persistence of seizures and profound ID. Trio exome sequencing identified a missense NSF variant (c.1688C>T / p.Pro563Leu) also confirmed and shown to be de novo by Sanger sequencing. Again the variant was absent from public datasets and had a CADD score of 34. While expression of wt NSF allele in the developing eye of Drosophila had no effect, expression of mutants severely affected eye development - suggesting a dominant negative effect. NSF encodes a homo-hexameric AAA ATPase, which is recruited by SNAPs (Soluble NSF Attachment Proteins) - and the latter by SNAREs (SNAP REceptors) - thus having a role in vesicular transport and membrane fusion. There is currently no associated phenotype in OMIM/G2P. Overall, this gene could be considered for inclusion probably with amber/red rating pending further evidence (eg. additional work-up or alternative causes/explanations not discussed). Sources: Literature |
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| Intellectual disability v2.1098 | NSF |
Konstantinos Varvagiannis gene: NSF was added gene: NSF was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: NSF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NSF were set to 31675180 Phenotypes for gene: NSF were set to Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability Penetrance for gene: NSF were set to unknown Mode of pathogenicity for gene: NSF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: NSF was set to AMBER Added comment: Suzuki et al. (2019 - PMID: 31675180) report on 2 unrelated individuals with de novo missense NSF variants. Overall the phenotype corresponded to an early infantile epileptic encephalopathy. The first patient developed vomiting and tonic seizures immediately after birth, with burst-suppression pattern upon EEG. Trio exome sequencing, followed by Sanger sequencing of proband and parents, revealed a de novo missense variant (NM_006178.3:c.1375G>A / p.Ala459Thr), absent from public databases and predicted in silico to be deleterious (CADD score of 30). The girl died 36 days after birth due to respiratory failure. Another subject, having necessitated mechanical ventilation due to absence of spontaneous respiration after birth, developed myoclonic seizures. EEG showed a burst-suppression pattern. At the age of 3, she was noted to have persistence of seizures and profound ID. Trio exome sequencing identified a missense NSF variant (c.1688C>T / p.Pro563Leu) also confirmed and shown to be de novo by Sanger sequencing. Again the variant was absent from public datasets and had a CADD score of 34. While expression of wt NSF allele in the developing eye of Drosophila had no effect, expression of mutants severely affected eye development - suggesting a dominant negative effect. NSF encodes a homo-hexameric AAA ATPase, which is recruited by SNAPs (Soluble NSF Attachment Proteins) - and the latter by SNAREs (SNAP REceptors) - thus having a role in vesicular transport and membrane fusion. There is currently no associated phenotype in OMIM/G2P. Overall, this gene could be considered for inclusion probably with amber/red rating pending further evidence (eg. additional work-up or alternative causes/explanations not discussed). Sources: Literature |
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| Intellectual disability v2.1098 | WDFY3 | Konstantinos Varvagiannis reviewed gene: WDFY3: Rating: GREEN; Mode of pathogenicity: None; Publications: 27008544, 31327001, 25198012, 28191889; Phenotypes: ?Microcephaly 18, primary, autosomal dominant - MIM 617520; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.405 | SCAMP5 |
Konstantinos Varvagiannis gene: SCAMP5 was added gene: SCAMP5 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: SCAMP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SCAMP5 were set to 31439720; 20071347 Phenotypes for gene: SCAMP5 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of nervous system morphology; Behavioral abnormality Penetrance for gene: SCAMP5 were set to unknown Mode of pathogenicity for gene: SCAMP5 was set to Other Review for gene: SCAMP5 was set to AMBER Added comment: PMID: 31439720 (Hubert et al. 2019) reported on 2 unrelated individuals with severe ID, seizures, behavioral and brain MRI abnormalities (white matter hyperintensity and mesial temporal sclorosis), both harboring the same missense SCAMP5 mutation as a de novo event (NM_001178111.1:c.538G>T or p.Gly180Trp). Previously aCGH +/- metabolic workup were non diagnostic. The occurrence of the same de novo variant in both as well as the similar presentation (incl. MRI images) suggested SCAMP5 as the most probable candidate gene, despite presence of few other variants in both. SCAMP5 is highly expressed in brain (https://www.proteinatlas.org/ENSG00000198794-SCAMP5) and previous studies have suggested a role in synaptic vesicle trafficking (PMIDs cited: 29562188, 25057210, etc). Cultured skin fibroblasts from affected individuals failed to express SCAMP5. Scamp is the Drosophila orthologue, with previous studies having demonstrated that mutants display defects in climbing, olfactory-assisted memory and susceptibility to heat induced seizures (PMIDs cited: 25478561, 19144841). Expression of the Scamp Gly302Trp variant in Drosophila ('equivalent' to the SCAMP5 Gly180Trp) revealed strongly reduced levels for the variant compared with wt upon Western Blot, either due to reduced expression or due to increased turnover. Overall the effect of Gly302Trp expression was similar to Scamp knockdown by RNAi (eg. rough eye phenotype, reduced ability to climb the walls of a graded tube after tapping, less/no flies reaching adult stage) but significantly different compared to wt. As a result, a dominant-negative effect was presumed. ---------- PMID: 20071347 (Castermans et al. 2010) is cited as a previous report of a relevant affected individual. In this study a 40 y.o. male with early DD, mild ID (IQ of 63) and ASD was found to harbor a de novo apparently balanced t(1;15) translocation affecting CLIC4 and PPCDC (both not associated with ID). [1-Mb resolution aCGH revealed no relevant CNVs]. Studies were however focused on SCAMP5 given that the gene is located downstream of / proximal to PPCDC, has brain-enriched expression as well as involvement in synaptic trafficking and demonstrated: - Less than 50% expression upon quantitative RT-PCR in patients leukocytes, compared to control. - Silencing and overexpression of Scamp5 in mouse β-TC3 cells resulted in increased and suppressed respectively secretion of large dense-core vesicles (LDCVs). - Given conservation of some components involved in secretion of dense core granules (DCGs) in platelets and LDCVs in neuronal cells, study of patient platelets - where SCAMP5 was confirmed to be expressed - suggested an altered pattern of DCGs. ---------- SCAMP5 is not associated with any phenotype in OMIM/G2P/SysID and not commonly included in gene panels for ID. ---------- Overall, this gene could be considered for inclusion in the ID and epilepsy panels probably with amber (# of unrelated individuals, 1 recurrent de novo variant and 1 regulatory effect, gene expressed in brain with a role in synaptic vesicle trafficking) or red rating (pending further evidence). Sources: Literature |
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| Intellectual disability v2.1098 | SCAMP5 |
Konstantinos Varvagiannis gene: SCAMP5 was added gene: SCAMP5 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: SCAMP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SCAMP5 were set to 31439720; 20071347 Phenotypes for gene: SCAMP5 were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of nervous system morphology; Behavioral abnormality Penetrance for gene: SCAMP5 were set to unknown Mode of pathogenicity for gene: SCAMP5 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: SCAMP5 was set to AMBER Added comment: PMID: 31439720 (Hubert et al. 2019) reported on 2 unrelated individuals with severe ID, seizures behavioral and brain MRI abnormalities (white matter hyperintensity and mesial temporal sclorosis), both harboring the same missense SCAMP5 mutation as a de novo event (NM_001178111.1:c.538G>T or p.Gly180Trp). Previously aCGH +/- metabolic workup were non diagnostic. The occurrence of the same de novo variant in both as well as the similar presentation (incl. MRI images) suggested SCAMP5 as the most probable candidate gene, despite presence of few other variants in both. SCAMP5 is highly expressed in brain (https://www.proteinatlas.org/ENSG00000198794-SCAMP5) and previous studies have suggested a role in synaptic vesicle trafficking (PMIDs cited: 29562188, 25057210, etc). Cultured skin fibroblasts from affected individuals failed to express SCAMP5. Scamp is the Drosophila orthologue, with previous studies having demonstrated that mutants display defects in climbing, olfactory-assisted memory and susceptibility to heat induced seizures (PMIDs cited: 25478561, 19144841). Expression of the Scamp Gly302Trp variant in Drosophila ('equivalent' to the SCAMP5 Gly180Trp) revealed strongly reduced levels for the variant compared with wt upon Western Blot, either due to reduced expression or due to increased turnover. Overall the effect of Gly302Trp expression was similar to Scamp knockdown by RNAi (eg. rough eye phenotype, reduced ability to climb the walls of a graded tube after tapping, less/no flies reaching adult stage) but significantly different compared to wt. As a result, a dominant-negative effect was presumed. ---------- PMID: 20071347 (Castermans et al. 2010) is cited as a previous report of a relevant affected individual. In this study a 40 y.o. male with early DD, mild ID (IQ of 63) and ASD was found to harbor a de novo apparently balanced t(1;15) translocation affecting CLIC4 and PPCDC (both not associated with ID). [1-Mb resolution aCGH revealed no relevant CNVs]. Studies were however focused on SCAMP5 given that the gene is located downstream of / proximal to PPCDC, has brain-enriched expression as well as involvement in synaptic trafficking and demonstrated: - Less than 50% expression upon quantitative RT-PCR in patients leukocytes, compared to control. - Silencing and overexpression of Scamp5 in mouse β-TC3 cells resulted in increased and suppressed respectively secretion of large dense-core vesicles (LDCVs). - Given conservation of some components involved in secretion of dense core granules (DCGs) in platelets and LDCVs in neuronal cells, study of patient platelets - where SCAMP5 was confirmed to be expressed - suggested an altered pattern of DCGs. ---------- SCAMP5 is not associated with any phenotype in OMIM/G2P/SysID and not commonly included in gene panels for ID. ---------- Overall, this gene could be considered for inclusion in the ID and epilepsy panels probably with amber (# of unrelated individuals, 1 recurrent de novo variant and 1 regulatory effect, gene expressed in brain with a role in synaptic vesicle trafficking) or red rating (pending further evidence). Sources: Literature |
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| Intellectual disability v2.1098 | FAM160B1 |
Konstantinos Varvagiannis gene: FAM160B1 was added gene: FAM160B1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: FAM160B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM160B1 were set to 27431290; 31353455 Phenotypes for gene: FAM160B1 were set to Central hypotonia; Global developmental delay; Intellectual disability; Abnormality of the face Penetrance for gene: FAM160B1 were set to Complete Review for gene: FAM160B1 was set to AMBER Added comment: Anazi et al. (2017 - PMID: 27431290) in a study of 337 subjects with ID, reported on a consanguineous family (15DG2696) with 3 affected sibs. The proband, a 7 y.o. boy had hypotonia, DD, mild ID (IQ of 69), some facial dysmorphic features as well as increased skin elasticity and joint hypermobility. Initial investigations included metabolic testing for OA and CDGs, FMR1 and aCGH. A 4 y.o. sister and a 3 y.o. brother of the proband had similar presentation of DD. Exome sequencing, autozygosity mapping and segregation studies suggested a FAM160B1 hmz missense SNV as the likely causal variant (NM_001135051.1:c.248T>C or p.Leu83Pro). There were no other candidate variants. As the encoded protein has a yet unknown function, with uncertain in silico 3D modeling, the authors speculated disruption of helices affecting fold/(ligand binding) function as the underlying effect of this variant. Mavioğlu et al. (2019 - PMID: 31353455) reported on a 38 y.o. female with history of motor and language delay, severe ID, ataxia, behavioral abrnormalities as well as some dysmorphic features. This individual was born to consanguineous parents (2nd cousins). There was history of a deceased, similarly affected sib. Initial investigations included metabolic work-up (plasma AA, urinary OA) and karyotyping. SNP genotyping in the family (parents, affected sib, 3 unaffected sibs) and multipoint linkage analysis for AR inheritance, yielded a maximum LOD score of 2.15. Selection of homozygous regions unique to the patient (but not present in unaffected sibs) did not suggest any known ID gene. Exome sequencing of the proband, with analysis of the variants in candidate regions revealed a homozygous stopgain SNV (NM_020940.4:c.115G>T or p.Glu39*) as the best candidate variant (with few others not considered to be relevant). FAM160B1 has a pLI of 1, LoF variants in public databases have MAFs below 0.000034 with no recorded homozygotes. In silico predictions suggested a deleterious effect (CADD score of 40, etc). The previous report by Anazi and fulfilment of the ACMG criteria for its classification of this variant as pathogenic led to its consideration as causal of the patient's phenotype. Study of the expression of the 2 isoforms of the gene (isoform1: NM_020940, 2:NM_001135051) revealed that the first is ubiquitously expressed and the second only in testes. [To my understanding the 2 isoforms seem to differ only in their last exon, the 2 reported variants affecting both isoforms - http://genome.ucsc.edu/cgi-bin/hgTracks?db=hg19&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr10%3A116577123%2D116663023&hgsid=777553295_dPP9DgaheaF82gTRTfZO6XS5lEzA ] The function of this gene remains unknown. Animal models/phenotypes are probably not available. There is no associated phenotype in OMIM/G2P. SysID lists FAM160B1 as a candidate ID gene. FAM160B1 is not commonly included in gene panels for ID offered by diagnostic laboratories. As a result this gene can be considered for inclusion in the current panel probably with amber (2 families/variants, variable ID as a feature) or red rating pending further evidence (given the partial phenotypic overlap, unknown function of the gene, variants not further studied, no animal models). Sources: Literature |
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| Early onset or syndromic epilepsy v1.405 | PCYT2 |
Konstantinos Varvagiannis gene: PCYT2 was added gene: PCYT2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCYT2 were set to 31637422 Phenotypes for gene: PCYT2 were set to Global developmental delay; Developmental regression; Intellectual disability; Spastic paraparesis; Seizures; Cerebral atrophy; Cerebellar atrophy Penetrance for gene: PCYT2 were set to Complete Review for gene: PCYT2 was set to GREEN Added comment: Vaz et al. (2019 - PMID: 31637422 - DDD study among the co-authors) report on 5 individuals - from 4 families - with biallelic PCYT2 mutations. The phenotype corresponded to a complex hererditary paraplegia with global DD, regression (4/5), ID (mild in 3/5, severe in 2/5), spastic para-/tetraparesis, epilepsy (5/5 - variable onset 2-16 yrs - focal or tonic-clonic seizures) and progressive cerebral and cerebellar atrophy. Exome sequencing in all revealed biallelic PCYT2 variants, confirmed with Sanger s. in probands and their parents (NM_001184917.2 - corresponding to the canonical transcript used as Ref below): - P1 (Fam1) : 2 missense SNVs in trans configuration, c.730C>T or p.His244Tyr and c.920C>T or p.Pro307Leu - P2 (Fam2 - consanguineous of White British origin), P3 (Fam3 - Consanguineous of Turkish origin), P4,5 (Fam4 - consanguineous, unspecified origin) : homozygosity for c.1129C>T or p.Arg377Ter) affecting the last exon of 8/12 transcripts, including the canonical one. Individuals with the same genotype displayed variable degrees of ID (eg P3 - severe / P2, P4,5 - mild ID). For sibs in Fam4, homozygosity for a missense SACS variant led to consideration of the respective disorder (AR spastic ataxia of Charlevoix-Saguenay) though the variant was predicted to be tolerated in silico and notably the MRI images not suggestive. All variants were absent from / had extremely low AF in public databases, with no homozygotes. Posphatidylethanolamine (PE) is a membrane lipid, particularly enriched in human brain (45% of phospholypid fraction). PE is synthesized either via the CDP-ethanolamine pathway or by decarboxylation of phosphatidylserine in mitochondria. PCYT2 encodes CTP:phosophoethanolamine cytidyltransferase (ET) which is an ubiquitously expressed rate-limiting enzyme for PE biosynthesis in the former pathway. In silico, the 2 missense variants - localizing in the CTP catalytic domain 2 - were predicted to be damaging, as well as to affect protein stability. Fibroblasts of 3 patients (P1, P2, P3) representing all variants were studied: - Enzymatic activity was shown to be significantly reduced (though not absent) compared to controls. Abnormalities were noted upon Western Blot incl. absence in all 3 patients studied of one of the 2 bands normally found in controls (probably representing the longer isoform), reduced intensity in all 3 of another band probably corresponding to a shorter isoform, and presence of an additional band of intermediate molec. mass in patients with the truncating variant. - RT-PCR on mRNA from patient fibroblasts did not reveal (significant) reduction compared to controls. - Lipidomic profile of patient fibroblasts was compatible with the location of the block in the phospholipid biosynthesis pathway and different from controls. The lipidomic profile had similarities with what has been reported for EPT1 deficiency, the enzyme directly downstream of ET. The SELENO1-related phenotype (/EPT1 deficiency) is also highly overlapping. CRISPR-Cas9 was used to generate pcyt2 partial or complete knockout (ko) zebrafish, targeting either the final (ex13) or another exon (ex3) respectively. mRNA expression was shown to be moderately reduced in the first case and severely reduced/absent in the second, compared to wt. Similarly, complete-ko (ex3) led to significantly lower survival, with impaired though somewhat better survival of partial-ko (ex13) zebrafish. Complete knockout of Pcyt2 in mice is embryonically lethal (PMID cited: 17325045) while heterozygous mice develop features of metabolic syndrome (PMID cited: 22764088). Given lethality in knockout zebrafish / mice and the residual activity (15-20%) in patient fibroblasts, the variants reported were thought to be hypomorphic and complete loss of function possibly incompatible with life. PCYT2 is not associated with any phenotype in OMIM/G2P/SysID and not commonly included in gene panels for ID. As a result this gene could included in the ID / epilepsy panels with green (~/>3 indiv/fam/variants with the nonsense found in different populations, consistent phenotype, lipidomics, in silico/in vitro/in vivo evidence) or amber rating. [Please consider inclusion in other possibly relevant panels eg. for metabolic disorders, etc]. Sources: Literature |
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| Intellectual disability v2.1098 | PCYT2 |
Konstantinos Varvagiannis gene: PCYT2 was added gene: PCYT2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCYT2 were set to 31637422 Phenotypes for gene: PCYT2 were set to Global developmental delay; Developmental regression; Intellectual disability; Spastic paraparesis; Seizures; Spastic tetraparesis; Cerebral atrophy; Cerebellar atrophy Penetrance for gene: PCYT2 were set to Complete Review for gene: PCYT2 was set to GREEN Added comment: Vaz et al. (2019 - PMID: 31637422 - DDD study among the co-authors) report on 5 individuals - from 4 families - with biallelic PCYT2 mutations. The phenotype corresponded to a complex hererditary paraplegia with global DD, regression (4/5), ID (mild in 3/5, severe in 2/5), spastic para-/tetraparesis, epilepsy (5/5 - variable onset 2-16 yrs - focal or tonic-clonic seizures) and progressive cerebral and cerebellar atrophy. Exome sequencing in all revealed biallelic PCYT2 variants, confirmed with Sanger s. in probands and their parents (NM_001184917.2 - corresponding to the canonical transcript used as Ref below): - P1 (Fam1) : 2 missense SNVs in trans configuration, c.730C>T or p.His244Tyr and c.920C>T or p.Pro307Leu - P2 (Fam2 - consanguineous of White British origin), P3 (Fam3 - Consanguineous of Turkish origin), P4,5 (Fam4 - consanguineous, unspecified origin) : homozygosity for c.1129C>T or p.Arg377Ter) affecting the last exon of 8/12 transcripts, including the canonical one. Individuals with the same genotype displayed variable degrees of ID (eg P3 - severe / P2, P4,5 - mild ID). For sibs in Fam4, homozygosity for a missense SACS variant led to consideration of the respective disorder (AR spastic ataxia of Charlevoix-Saguenay) though the variant was predicted to be tolerated in silico and notably the MRI images not suggestive. All variants were absent from / had extremely low AF in public databases, with no homozygotes. Posphatidylethanolamine (PE) is a membrane lipid, particularly enriched in human brain (45% of phospholypid fraction). PE is synthesized either via the CDP-ethanolamine pathway or by decarboxylation of phosphatidylserine in mitochondria. PCYT2 encodes CTP:phosophoethanolamine cytidyltransferase (ET) which is an ubiquitously expressed rate-limiting enzyme for PE biosynthesis in the former pathway. In silico, the 2 missense variants - localizing in the CTP catalytic domain 2 - were predicted to be damaging, as well as to affect protein stability. Fibroblasts of 3 patients (P1, P2, P3) representing all variants were studied: - Enzymatic activity was shown to be significantly reduced (though not absent) compared to controls. Abnormalities were noted upon Western Blot incl. absence in all 3 patients studied of one of the 2 bands normally found in controls (probably representing the longer isoform), reduced intensity in all 3 of another band probably corresponding to a shorter isoform, and presence of an additional band of intermediate molec. mass in patients with the truncating variant. - RT-PCR on mRNA from patient fibroblasts did not reveal (significant) reduction compared to controls. - Lipidomic profile of patient fibroblasts was compatible with the location of the block in the phospholipid biosynthesis pathway and different from controls. The lipidomic profile had similarities with what has been reported for EPT1 deficiency, the enzyme directly downstream of ET. The SELENO1-related phenotype (/EPT1 deficiency) is also highly overlapping. CRISPR-Cas9 was used to generate pcyt2 partial or complete knockout (ko) zebrafish, targeting either the final (ex13) or another exon (ex3) respectively. mRNA expression was shown to be moderately reduced in the first case and severely reduced/absent in the second, compared to wt. Similarly, complete-ko (ex3) led to significantly lower survival, with impaired though somewhat better survival of partial-ko (ex13) zebrafish. Complete knockout of Pcyt2 in mice is embryonically lethal (PMID cited: 17325045) while heterozygous mice develop features of metabolic syndrome (PMID cited: 22764088). Given lethality in knockout zebrafish / mice and the residual activity (15-20%) in patient fibroblasts, the variants reported were thought to be hypomorphic and complete loss of function possibly incompatible with life. PCYT2 is not associated with any phenotype in OMIM/G2P/SysID and not commonly included in gene panels for ID. As a result this gene could included in the ID / epilepsy panels with green (~/>3 indiv/fam/variants with the nonsense found in different populations, consistent phenotype, lipidomics, in silico/in vitro/in vivo evidence) or amber rating. [Please consider inclusion in other possibly relevant panels eg. for metabolic disorders, etc]. Sources: Literature |
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| Intellectual disability v2.1098 | PDE6D |
Konstantinos Varvagiannis gene: PDE6D was added gene: PDE6D was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: PDE6D was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDE6D were set to 24166846; 30423442 Phenotypes for gene: PDE6D were set to ?Joubert syndrome 22 - MIM 615665 Penetrance for gene: PDE6D were set to Complete Review for gene: PDE6D was set to AMBER gene: PDE6D was marked as current diagnostic Added comment: Thomas et al. (2014 - PMID: 24166846) reported on a consanguineous Pakistani family with 3 members presenting variable polydactyly, brain anomalies (incl. molar tooth sign), microphthalmia/coloboma with retinal disease, renal hypoplasia suggestive of Joubert syndrome. Genotyping with a SNP array identified a unique 17-Mb region of homozygosity on chr2 with LOD score of 2.6. The region contained 208 genes, of which 15 present in ciliary gene databases. A homozygous splicing variant appeared to be the only relevant, PDE6D being a ciliary gene within this region [NM_002601.4:c.140-1G>A]. Status of all affected members, parents and 2 unaffected sibs was verified with Sanger sequencing. PDE6D encodes a phosphodiesterase that binds to prenyl groups and has a critical role in ciliogenesis (Humbert et al. - PMID: 23150559 and OMIM). Several lines of evidence provided support a role for PDE6D and the reported variants : - Study of PDE6D expression during human embryogenesis suggests ubiquitous localization and highest levels in organs affected in ciliopathies (CNS, kidney tubules, respiratory tract epitherlial cells). - RT-PCR of mRNA from control/patient fibroblasts and sequencing confirmed the splicing defect leading to an in-frame deletion of exon 3. - Wt and mutant protein both localized in the basal body of primary cilia (patient/control fibroblasts). Cilia in both cases had normal morphology. - Experiments in RPE cells confirmed that INPP5E (involved in Joubert/MORM syndrome) interacts (/is probably a cargo of) PDE6D, a process dependent on prenylation. - Exon 3 deletion was confirmed to disrupt PDE6D binding to INPP5E. - Analysis by immunofluoresence of INPP5E localization using control/patient fibroblasts and renal tissue showed absence of INPP5E from primary cilia in the case of patient cells (but not controls) suggesting that PDE6D is important for trafficking INPP5E to the cilium. - Previous study in mice suggested altered photoreceptor physiology in Pde6d (-/-) animals, resulting in a slowly progressing rod/cone dystrophy. The effect was however limited to the eye. (PMID cited : 17496142 - Zhang et al., 2007). - Morpholino knockdown of pde6d resulted in pericardial edema, eye abnormalities (microphthalmia and disorganized retinal cell layers) and kidney morphogenesis defects (distended, blocked pronephric openings and proximal tubule cysts). Edema was rescued upon coinjection of morpholino with wt (but not mutant) mRNA. Similarly coinjection led to complete or partial rescue of eye development in the case of wt and mutant mRNA respectively supporting pathogenicity and (partial) loss-of-function effect for the variant. --------- Mégarbané et al. (2019 - PMID: 30423442) reported on an affected 6 month-old boy born to Lebanese first-cousin parents. Features included hypotonia, developmental delay, microcephaly, oculomotor apraxia, postaxial polydactyly of hands and feet and presence of a molar tooth sign upon brain MRI. Renal and retinal anomalies were absent (also given his age). Exome sequencing revealed homozygosity for a frameshift PDE6D variant [NM_002601.3:c.367_368insG or p.(Leu123Cysfs*13)]. Sanger sequencing confirmed presence of the variant in the proband and carrier status of the parents. The variant affected the penultimate exon (note : present in only this longest transcript) and was not predicted to trigger NMD but rather lead to elimination of a highly conserved PDZ-interaction domain. --------- The phenotype associated with biallelic PDE6D variants in OMIM is ?Joubert syndrome 22 - MIM 615665 based only on the 1st report ('delayed psychomotor development' among the features). There is no relevant entry in G2P. PDE6D is listed as a Current primary (/confirmed) ID gene in SysID (the aforementioned PMIDs cited). This gene is included in gene panels for ID offered by some diagnostic laboratories (eg. GeneDx). --------- Overall PDE6D could be considered for inclusion in the ID panel probably with amber rating (2 families/variants, DD but outcome otherwise unknown - evidence for the the gene causing JS seems however sufficient). Sources: Literature |
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| Intellectual disability v2.1098 | NTNG2 |
Konstantinos Varvagiannis gene: NTNG2 was added gene: NTNG2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: NTNG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NTNG2 were set to 31372774; 31668703 Phenotypes for gene: NTNG2 were set to Central hypotonia; Global developmental delay; Intellectual disability; Behavioral abnormality; Microcephaly; Seizures Penetrance for gene: NTNG2 were set to Complete Review for gene: NTNG2 was set to GREEN Added comment: [1] Abu-Libdeh et al. (2019 - PMID: 31372774) reported 8 individuals from 4 unrelated consanguineous families of Arab Muslim origin, all homozygous for NM_032536.3:c.376dup - p.(Ser126PhefsTer241). Common features included hypotonia, failure to achieve milestones and developmental stagnation without regression during the first year (~9m) of life and severe ID. Minimal purposeful hand use (grasping and bringing objects to mouth), hand stereotypies and bruxism were also observed. Microcephaly and impaired growth were almost universal (with the exception of 2 having an OFC at ~10% percentile). Relevant previous investigations were normal in all and included MECP2, SMN1, aCGH, metabolic testing, etc. The variant was identified by exome in all, and Sanger confirmed with compatible segregation studies in parents and sibs. The variant was found within a shared haplotype of ~4.35 Mb, probably due to a founder effect. [2] Dias et al. (2019 - PMID: 31668703) described 16 individuals from 7 unrelated families from Iran, Mexico, Turkey, Egypt and Bangladesh. Parents were known to be consanguineous or shown to be distantly related. All patients were homozygous for missense variants private to each family (7 variants) identified following exome sequencing. Shared features incl. hypotonia, GDD, severe to profound ID and behavioral anomalies incl. autistic features/stereotypies (most), screaming/laughing spells (most), bruxism. Microcephaly (5/14), growth below average/FTT and GI problems were also observed. Epilepsy was reported in 5 individuals belonging to 4 different families in these 2 studies (5/24 overall / 4 variants). Netrin-G2, the encoded protein, is bound to the plasma membrane by GPI-anchors. Netrins-G2 and G1 (another member of the Netrin-G subfamily) are enriched in presynaptic terminals. Interaction with their cognate Netrin-G ligand trans-synaptic partners / receptors (NGL2, NGL1 respectively) has been shown to promote axon outgrowth, induce and maintain excitatory synapse formation. Complementary and non-overlapping expression in the developping and mature CNS has been shown for Netrin-G2/1 in mice (several references provided by Abu-Libdeh / Dias). Variant effect : The frameshift variant was not studied by Abu-Libdeh et al. Variants in the 2nd ref. were all missense, displayed no-specific localization and were suggested to affect protein stability and/or expression at the cell surface as 4/7 involved loss or addition of cystein residues (possibly creating unpaired cysteins) and 2 of the remaining 3 were predicted to affect the hydrophobic core. In line with this, overexpression of wt/variant constructs in HeLa cells demonstrated substantially decreased cell surface expression for all variants. Mouse models/phenotypes : Dias et al. showed that siRNA-mediated Ntng2 knockdown in N2a cells led to significant reduction in neurite number and length. Studied previously, Ntng2 knockout mice display impaired learning, memory, visual and motor functioning (PMID cited : 26746425). NTNG2 is not associated with any phenotype in OMIM/G2P. SysID lists it among the candidate ID genes, citing PMID: 29302074 (not here reviewed & NTNG2 not in the main text). Overall this gene can be considered for inclusion in the ID panel probably as green (>3 individuals/families/variants, consistent phenotype in both reports, role of the gene, in silico and in vitro studies, animal model, etc) or amber. [Please consider inclusion in other panels if relevant eg. ASD panel (many individuals having autistic / Rett-like features or epilepsy) or epilepsy (>3 individuals/families/variants although most families were also consanguineous)] Sources: Literature |
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| Intellectual disability v2.1098 | AP1B1 |
Konstantinos Varvagiannis gene: AP1B1 was added gene: AP1B1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: AP1B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AP1B1 were set to 31630788; 31630791 Phenotypes for gene: AP1B1 were set to Failure to thrive; Abnormality of the skin; Hearing abnormality; Abnormality of copper homeostasis; Global developmental delay; Intellectual disability Penetrance for gene: AP1B1 were set to Complete Review for gene: AP1B1 was set to AMBER Added comment: Boyden et al. (2019 - PMID: 31630788) and Alsaif et al (2019 - PMID: 31630791) report on the phenotype related to biallelic AP1B1 mutations. Common features included failure to thrive, ichthyosis (with variable palmoplantar keratoderma/erythroderma/abnormal hair) and hearing loss. Each study focused on different additional features eg. thrombocytopenia or photophobia in all individuals reported by Boyden et al, while Alsaif et al. focused on abnormal copper metabolism (low plasma copper and ceruloplasmin) observed in all 3 affected individuals and enteropathy/hepatopathy observed in 2 sibs. DD was observed in all 3 individuals (2 families) reported by Alsaif et al. and patient 424 reported by Boyden et al. ID was noted in all individuals of relevant age (2 from 2 families) in the study by Alsaif. Boyden commented that ID is not part of the phenotype. The adult (424) - despite his early DD - was noted to have normal intellect and had graduated college. The other patient (1325) was last followed up at 11 months (still DD was not reported). AP1B1 encodes one of the large subunits (β1) of the adaptor protein complex 1. Each of the AP complexes is a heterotetramer composed of two large (one of γ, α, δ, ε and β1-β4 for AP-1 to AP-4 respectively), one medium (μ1-μ4) and one small (σ1-σ4) adaptin subunit. The complex is involved in vesicle-mediated transport. Variants were confirmed in probands and carrier parents (NM_001127.3): Boyden Pat424 (33y) : c.430T>C (p.Cys144Arg) in trans with c.2335delC (p.Leu779Serfs*26) Boyden Pat1325 (11m) [consanguineous Ashkenazi Jewish family] : homozygosity for c.2374G>T (p.Glu792*) Alsaif sibs P1,P2 (4y4m, 1y5m) [consanguineous - Pakistani origin] : homozygous for a chr22 75 kb deletion spanning only the promoter and ex1-2 of AP1B1 Alsaif P3 (4y6m) [consanguineous - Saudi origin] : homozygous for a c.38-1G>A Variant / additional studies : 22q 75-kb deletion: PCR deletion mapping and Sanger delineated the breakpoints of the 22q12.2 del to chr22:29758984-29815476 (hg?). Complete absence of transcript upon RT-PCR (mRNA from fibrolasts). Splicing variant (c.38-1G>A): RT-PCR confirmed replacement of the normal transcript by an aberrant harboring a 1 bp deletion (r.40del). Stopgain variant (c.2374G>T): Western blot demonstrated loss of AP1B1 (and marked reduction also for AP1G1) in cultured keratinocytes of the homozygous patient. Loss-of-function is the effect predicted by variants. Vesicular defects were observed in keratinocytes of an affected individual (homozygous for the nonsense variant). Rescue of these vesicular defects upon transduction with wt AP1B1 lentiviral construct confirmed the LoF effect. [Boyden et al.] ATP7A and ATP7B, two copper transporters, have been shown to depend on AP-1 for their trafficking. Similar to MEDNIK syndrome, caused by mutations in AP1S1 and having an overlapping phenotype with AP1B1 (also including hypocupremia and hypoceruloplasminemia), fibroblasts from 2 affected individuals (from different families) demonstrated abnormal ATP7A trafficking. [Alsaif et al.] Proteomic analysis of clathrin coated vesicles (2 ind from 2 fam) demonstrated that AP1B1 was the only AP1/AP2 CCV component consistently reduced in 2 individuals (from 2 families). [Alsaif et al.] Boyden et al. provided evidence for abnormal differentiation and proliferation in skin from an affected individual. In addition E-cadherin and β-catenin were shown to be mislocalized in keratinocytes from this affected individual. Loss of ap1b1 in zebrafish is not lethal but lead to auditory defects (/vestibular deficits). The inner ears appear to develop normally, although there is progressive degeneration of ear epithelia. There are no behavioral/neurological phenotypes listed for mouse models. [ http://www.informatics.jax.org/marker/MGI:1096368 ]. AP1B1 is not associated with any phenotype in OMIM/G2P/SysID. Overall this gene could be considered for inclusion in the ID panel probably with amber rating. Sources: Literature |
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| Early onset or syndromic epilepsy v1.405 | FDFT1 |
Konstantinos Varvagiannis gene: FDFT1 was added gene: FDFT1 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: FDFT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FDFT1 were set to 29909962 Phenotypes for gene: FDFT1 were set to Profound global developmental delay; Intellectual disability; Seizures; Abnormality of nervous system morphology; Cortical visual impairment; Abnormality of the skin; Abnormality of the face Penetrance for gene: FDFT1 were set to Complete Review for gene: FDFT1 was set to AMBER Added comment: Biallelic pathogenic FDFT1 variants cause Squalene synthase deficiency (MIM 618156). 3 individuals from 2 families (and 3 variants) have been reported. DD, ID and seizures are part of the phenotype (3/3). The metabolic profile observed is specific and highly suggestive of disruption of the cholesterol biosynthesis pathway (at the specific level) while the clinical presentation is similar to other disorders of the pathway (SLO). The effect of 2 variants has been studied in detail (in one case mis-splicing demonstrated and in the other regulatory effect). Overall, this gene could be considered for inclusion in the ID/epilepsy panel with amber rating. As the gene is currently present only in the DDG2P panel, please consider adding it to relevant ones (eg. IEMs, undiagnosed metabolic disorders, etc). [Details provided below]. ---- Coman et al. (2018 - PMID: 29909962) reported on 3 relevant individuals from 2 unrelated families. The phenotype consisted of seizures (3/3 - neonatal onset - generalized), profound DD (ID can be inferred from the description in the supplement), variable brain MRI abnormalities (white matter loss, hypoplastic CC), cortical visual impairment, dry skin with photosensitivity as well facial dysmorphic features. Male subjects presented genital anomalies (cryptorchidism/hypospadias). FDFT1 encodes squalene synthase, the enzyme which catalyzes conversion of farnesyl-pyrophosphate to squalene - the first specific step in cholesterol biosynthesis. A specific pattern of metabolites was observed in all, similar to a pattern previously observed in animal models/humans treated with squalene synthase inhibitor or upon loading with farnesol (in animals). Overall the pattern was suggestive of a cholesterol biosynthesis defect at the level of squalene synthase as suggested by increased total farnesol levels (farnesyl-pyrophosphate + free farnesol), reduced/normal squalene, low plasma cholesterol as well as other metabolites. Clinical features also resembled those observed in Smith-Lemli-Opitz syndrome (another disorder of cholesterol biosynthesis). WES was carried out in affected individuals and their parents and revealed for sibs of the first family, compound heterozygosity for a maternally inherited 120-kb deletion spanning exons 6-10 of FDFT1 and CTSB and a paternally inherited FDFT1 variant in intron 8 (TC deletion/AG insertion). Variant studies for the latter included: - Minigene splice assay demonstrating retention of 22 bp in intron 8. - Partial splicing defect with both nl and mis-spliced cDNA (patient fibroblasts) - Reduced protein levels in lymphoblasts/fibroblasts from both sibs upon Western blot. Contribution of the CTSB deletion was considered unlikely (carrier mother was unaffected). As for the 2nd family, WES data allowed identification of a homozygous deep-intronic (although this is transcript-specific) 16-bp deletion in the proband. Parents were carriers. For the specific variant : - cDNA studies failed to detect 3 (of 10) isoforms which are normally present in control fibroblasts. Eventual NMD (which would be predicted if the deletion resulted in splicing defect) was eliminated given the absent effect of cyclohexamide addition, thus suggesting a regulatory effect. - Given a predicted promoter/enhancer effect of the deleted region, a luciferase assay performed, suggested that the sequence had promoter capacity, with the construct containing the 16-bp deletion showing reduced promoter activity. Fdft1 knockout mice demonstrate embryonic lethality around mid-gestation while they exhibit severe growth retardation and defective neural tube closure. In G2P FDFT1 is associated with 'Defect in Cholesterol Biosynthesis' (confidence:possible/biallelic/LoF). The gene belongs to the Current primary ID gene group of SysID. It is not commonly included in gene panels for ID offered by diagnostic laboratories. Sources: Literature |
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| Intellectual disability v2.1098 | FDFT1 |
Konstantinos Varvagiannis gene: FDFT1 was added gene: FDFT1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: FDFT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FDFT1 were set to 29909962 Phenotypes for gene: FDFT1 were set to Profound global developmental delay; Intellectual disability; Seizures; Abnormality of nervous system morphology; Cortical visual impairment; Abnormality of the skin; Abnormality of the face Penetrance for gene: FDFT1 were set to Complete Review for gene: FDFT1 was set to AMBER Added comment: Biallelic pathogenic FDFT1 variants cause Squalene synthase deficiency (MIM 618156). 3 individuals from 2 families (and 3 variants) have been reported. DD, ID and seizures are part of the phenotype (3/3). The metabolic profile observed is specific and highly suggestive of disruption of the cholesterol biosynthesis pathway (at the specific level) while the clinical presentation is similar to other disorders of the pathway (SLO). The effect of 2 variants has been studied in detail (in one case mis-splicing demonstrated and in the other regulatory effect). Overall, this gene could be considered for inclusion in the ID/epilepsy panel with amber rating. As the gene is currently present only in the DDG2P panel, please consider adding it to relevant ones (eg. IEMs, undiagnosed metabolic disorders, etc). [Details provided below]. ---- Coman et al. (2018 - PMID: 29909962) reported on 3 relevant individuals from 2 unrelated families. The phenotype consisted of seizures (3/3 - neonatal onset - generalized), profound DD (ID can be inferred from the description in the supplement), variable brain MRI abnormalities (white matter loss, hypoplastic CC), cortical visual impairment, dry skin with photosensitivity as well facial dysmorphic features. Male subjects presented genital anomalies (cryptorchidism/hypospadias). FDFT1 encodes squalene synthase, the enzyme which catalyzes conversion of farnesyl-pyrophosphate to squalene - the first specific step in cholesterol biosynthesis. A specific pattern of metabolites was observed in all, similar to a pattern previously observed in animal models/humans treated with squalene synthase inhibitor or upon loading with farnesol (in animals). Overall the pattern was suggestive of a cholesterol biosynthesis defect at the level of squalene synthase as suggested by increased total farnesol levels (farnesyl-pyrophosphate + free farnesol), reduced/normal squalene, low plasma cholesterol as well as other metabolites. Clinical features also resembled those observed in Smith-Lemli-Opitz syndrome (another disorder of cholesterol biosynthesis). WES was carried out in affected individuals and their parents and revealed for sibs of the first family, compound heterozygosity for a maternally inherited 120-kb deletion spanning exons 6-10 of FDFT1 and CTSB and a paternally inherited FDFT1 variant in intron 8 (TC deletion/AG insertion). Variant studies for the latter included: - Minigene splice assay demonstrating retention of 22 bp in intron 8. - Partial splicing defect with both nl and mis-spliced cDNA (patient fibroblasts) - Reduced protein levels in lymphoblasts/fibroblasts from both sibs upon Western blot. Contribution of the CTSB deletion was considered unlikely (carrier mother was unaffected). As for the 2nd family, WES data allowed identification of a homozygous deep-intronic (although this is transcript-specific) 16-bp deletion in the proband. Parents were carriers. For the specific variant : - cDNA studies failed to detect 3 (of 10) isoforms which are normally present in control fibroblasts. Eventual NMD (which would be predicted if the deletion resulted in splicing defect) was eliminated given the absent effect of cyclohexamide addition, thus suggesting a regulatory effect. - Given a predicted promoter/enhancer effect of the deleted region, a luciferase assay performed, suggested that the sequence had promoter capacity, with the construct containing the 16-bp deletion showing reduced promoter activity. Fdft1 knockout mice demonstrate embryonic lethality around mid-gestation while they exhibit severe growth retardation and defective neural tube closure. In G2P FDFT1 is associated with 'Defect in Cholesterol Biosynthesis' (confidence:possible/biallelic/LoF). The gene belongs to the Current primary ID gene group of SysID. It is not commonly included in gene panels for ID offered by diagnostic laboratories. Sources: Literature |
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| Intellectual disability v2.1098 | IQSEC1 |
Konstantinos Varvagiannis gene: IQSEC1 was added gene: IQSEC1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: IQSEC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IQSEC1 were set to 31607425 Phenotypes for gene: IQSEC1 were set to Central hypotonia; Global developmental delay; Intellectual disability; Behavioral abnormality; Short stature Penetrance for gene: IQSEC1 were set to Complete Review for gene: IQSEC1 was set to AMBER Added comment: Ansar et al. (2019 - PMID: 31607425) reported on 5 individuals with biallelic IQSEC1 variants. Common features included hypotonia, DD, speech impairment, severe ID, behavioral problems as well as short stature. Early-onset seizures were observed in 3 sibs (for whom there was also a paternal family history of seizures). These subjects belonging to 2 consanguineous families from Pakistan and S. Arabia were found to harbor homozygous missense variants private to each family (Fam1: NM_001134382.2:c.1028C>T or p.Thr354Met following SNP genotyping of several members and exome of the proband | Fam2: c.962G>A or p.Arg321Gln following exome in 2 affected members). Sanger confirmation and study of parents (+/- sibs) were compatible. The homozygous variant was the only candidate in the 1st family (also following exclusion of other causes of ID/short stature), and most likely/compatible with the patient's phenotype in the 2nd. As the authors note, IQSEC1-3 encode guanine exchange factors (GEFs) for the ARF family of GTPases. IQSEC2 is a known XLID gene, while biallelic IQSEC3 mutations in ID have been recently reported (PMID: 31130284), all presenting phenotypic similarities (ID, short stature, speech defect). Previous studies cited had shown that IQSEC1 & 2 are concentrated at the postsynaptic density of glutamatergic synapses in mammalian brain, playing a role in actin-dependent processes incl. AMPA receptor trafficing at synapses (all refs in article). Drosophila model: The ortholog of IQSEC1, 2 and 3 is schizo and the phenotype associated with its loss is a growth cone guidance defect through dysregulation of the Slit-Robo pathway (all refs in article). The authors studied overexpression of either reference IQSEC1 cDNA or variant cDNAs in wt flies, the former only being toxic/lethal. Loss of schizo was also embryonically lethal but was partially rescued by expression of reference IQSEC1 cDNA. Expression of cDNA for the 2 variants did not rescue lethality. As a result LoF appears to be the underlying effect of both variants. The authors provided evidence that schizo is localized in glia and neurons at various stages of development and is important for proper axon guidance in both CNS and PNS. In Drosophila, schizo is also localized in photoreceptors and RNAi-mediated knockdown resulted in severely impaired sight (also observed in 1 patient). Mouse model: Through generation of Iqsec1-floxed mice, it was demonstrated that targeted depletion of Iqsec1 in the cortex resulted in increased density/immature morphology of dendritic spines. IQSEC1 is not associated with any phenotype in OMIM / G2P / SysID and not commonly included in gene panels for ID. As a result, this gene could be considered for inclusion in the ID panel as probably as amber (2 families/variants). Sources: Literature |
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| Bilateral congenital or childhood onset cataracts v2.1 | PIK3C2A | Ivone Leong edited their review of gene: PIK3C2A: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bilateral congenital or childhood onset cataracts v2.1 | PIK3C2A |
Ivone Leong changed review comment from: PIK3C2A is associated with a relevant phenotype on OMIM but not on Gene2Phenotype. PMID: 31034465 describes 3 unrelated consanguineous families (Muslim-Arab Isreali, Tunisian and Syrian) with different homozygous variants in this gene. All affected members have similar features, which included "dysmorphic facial features, short stature, skeletal and neurological abnormalities, and cataracts". Therefore, this gene is appropriate for this panel and there is enough evidence for this gene to be promoted to Green status. Sources: Literature; to: PIK3C2A is associated with a relevant phenotype on OMIM but not on Gene2Phenotype. PMID: 31034465 describes 3 unrelated consanguineous families (Muslim-Arab Isreali, Tunisian and Syrian) with different homozygous variants in this gene. All affected members have similar features, which included "dysmorphic facial features, short stature, skeletal and neurological abnormalities, and cataracts". Therefore, this gene is appropriate for this panel and there is enough evidence for this gene to be promoted to Green status. Sources: Literature |
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| Bilateral congenital or childhood onset cataracts v2.1 | PIK3C2A |
Ivone Leong gene: PIK3C2A was added gene: PIK3C2A was added to Cataracts. Sources: Literature Mode of inheritance for gene: PIK3C2A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIK3C2A were set to 31034465 Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome, 618440 Review for gene: PIK3C2A was set to RED Added comment: PIK3C2A is associated with a relevant phenotype on OMIM but not on Gene2Phenotype. PMID: 31034465 describes 3 unrelated consanguineous families (Muslim-Arab Isreali, Tunisian and Syrian) with different homozygous variants in this gene. All affected members have similar features, which included "dysmorphic facial features, short stature, skeletal and neurological abnormalities, and cataracts". Therefore, this gene is appropriate for this panel and there is enough evidence for this gene to be promoted to Green status. Sources: Literature |
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| Intellectual disability v2.1098 | TAOK1 | Rebecca Foulger Phenotypes for gene: TAOK1 were changed from to INTELLECTUAL DISABILITY; developmental delay | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1097 | TAOK1 | Rebecca Foulger Publications for gene: TAOK1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1096 | TAOK1 | Rebecca Foulger Added comment: Comment on mode of inheritance: Set MOI to MONOALLELIC, to match Gene2Phenotype and PMID:31230721. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1096 | TAOK1 | Rebecca Foulger Mode of inheritance for gene: TAOK1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1095 | TAOK1 | Ellen McDonagh reviewed gene: TAOK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31230721; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rare syndromic craniosynostosis or isolated multisuture synostosis v2.0 | FBN1 |
Eleanor Williams commented on gene: FBN1: PMID: 16596670 - Ades et al 2006 - report 2 patients with heterozygous FBN1 mutations (Patients 1 and 2) and a patient with a heterozygous FBN1 deletion (Patient 5). Patient 1 had Marfan syndrome with scaphocephaly, unusually rounded orbital rims and recession of the right orbital and frontal regions. Coronal sutures were indistinct. The anterior half of the sagittal suture was fused. Patient 2 had severe early onset Marfan sydnrome and plagiocephaly with coronal, lambdoid, and sagittal sutures. Patient 5 had marfanoid (MD) features, mental retardation (MR), and dolichocephaly. PMID: 27884935 - Miller et al 2017 - report a case of a patient with craniosynostosis and a de novo splice variant affecting FBN1. c.8226+5G>A. |
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| Rare syndromic craniosynostosis or isolated multisuture synostosis v2.0 | MASP1 |
Eleanor Williams changed review comment from: PMID: 21258343 - Rooryck et al 2011 - report 1 patient with a homozygous MASP1variant ( c.1489 C>T, p.His497Tyr) that segregated with 3MC syndrome in the family. The patient's features included craniosynostosis. PMID: 26789649 - Urquhart et al 2016 - report 2 patients with homozygous variants in MASP1 (c.760A>T,p.(Leu 254*) and c.547G>T, p(.Val 183Leu) ) who have plagiocephaly and turricephaly respectively, but they note that craniosynostosis was not observed.; to: PMID: 21258343 - Rooryck et al 2011 - report 1 patient with a homozygous MASP1variant ( c.1489 C>T, p.His497Tyr) that segregated with 3MC syndrome in the family. The patient's features included craniosynostosis. PMID: 26789649 - Urquhart et al 2016 - report two 3MC syndrome patients with homozygous variants in MASP1 (c.760A>T,p.(Leu 254*) and c.547G>T, p(.Val 183Leu) ) who have plagiocephaly and turricephaly respectively, but they note that craniosynostosis was not observed. |
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| Rare syndromic craniosynostosis or isolated multisuture synostosis v2.0 | MASP1 |
Eleanor Williams commented on gene: MASP1: PMID: 21258343 - Rooryck et al 2011 - report 1 patient with a homozygous MASP1variant ( c.1489 C>T, p.His497Tyr) that segregated with 3MC syndrome in the family. The patient's features included craniosynostosis. PMID: 26789649 - Urquhart et al 2016 - report 2 patients with homozygous variants in MASP1 (c.760A>T,p.(Leu 254*) and c.547G>T, p(.Val 183Leu) ) who have plagiocephaly and turricephaly respectively, but they note that craniosynostosis was not observed. |
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| Intellectual disability v2.1095 | TAOK1 | Ellen Thomas Classified gene: TAOK1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1095 | TAOK1 | Ellen Thomas Added comment: Comment on list classification: Recently reported DD gene | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1095 | TAOK1 | Ellen Thomas Gene: taok1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1095 | TAOK1 | Ellen Thomas Classified gene: TAOK1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1095 | TAOK1 | Ellen Thomas Added comment: Comment on list classification: Recently reported DD gene | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1095 | TAOK1 | Ellen Thomas Gene: taok1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1095 | TAOK1 | Ellen Thomas Classified gene: TAOK1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1095 | TAOK1 | Ellen Thomas Added comment: Comment on list classification: Recently reported DD gene | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1095 | TAOK1 | Ellen Thomas Gene: taok1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1094 | TAOK1 | Ellen Thomas Classified gene: TAOK1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1094 | TAOK1 | Ellen Thomas Added comment: Comment on list classification: Recently reported DD gene | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1094 | TAOK1 | Ellen Thomas Gene: taok1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1094 | TAOK1 | Ellen Thomas Classified gene: TAOK1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1094 | TAOK1 | Ellen Thomas Added comment: Comment on list classification: Recently reported DD gene | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1094 | TAOK1 | Ellen Thomas Gene: taok1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.26 | CNBP_CCTG |
Louise Daugherty changed review comment from: STR added as part of the GMS. This STR is tested routinely using PCR-based methods in the NHS. It should be noted that this STR is currently not offered as part of the 100K RD Skeletal muscle channelopathy panel as is currently difficult to report this STR using the WGS EH pipeline because of the complex locus ( Sources: Expert list; to: STR added as part of the GMS. This STR is tested routinely using PCR-based methods in the NHS. It should be noted that this STR is currently not offered as part of the 100K RD Skeletal muscle channelopathy panel as is currently difficult to report this STR using the WGS EH pipeline because of the complex locus Sources: Expert list |
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| Skeletal muscle channelopathy v0.26 | CNBP_CCTG |
Louise Daugherty changed review comment from: STR added as part of the GMS. This STR is tested routinely using PCR-based methods in the NHS. Sources: Expert list; to: STR added as part of the GMS. This STR is tested routinely using PCR-based methods in the NHS. It should be noted that this STR is currently not offered as part of the 100K RD Skeletal muscle channelopathy panel as is currently difficult to report this STR using the WGS EH pipeline because of the complex locus ( Sources: Expert list |
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| Skeletal muscle channelopathy v0.26 | DMPK_CTG | Louise Daugherty Classified STR: DMPK_CTG as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.26 | DMPK_CTG | Louise Daugherty Str: dmpk_ctg has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.25 | DMPK | Louise Daugherty Classified gene: DMPK as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.25 | DMPK | Louise Daugherty Added comment: Comment on list classification: demoted to Red, this review is for the STR entity and not the gene entity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.25 | DMPK | Louise Daugherty Gene: dmpk has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.24 | DMPK_CTG |
Louise Daugherty STR: DMPK_CTG was added STR: DMPK_CTG was added to Myotonia congenita. Sources: Expert list Mode of inheritance for STR: DMPK_CTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: DMPK_CTG were set to 7825566 Phenotypes for STR: DMPK_CTG were set to Myotonic dystrophy 1, 16090 Review for STR: DMPK_CTG was set to GREEN Added comment: STR added as part of the GMS. This STR is tested routinely using PCR-based methods in the NHS. Sources: Expert list |
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| Skeletal muscle channelopathy v0.23 | CNBP_CCTG | Louise Daugherty Classified STR: CNBP_CCTG as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.23 | CNBP_CCTG | Louise Daugherty Str: cnbp_cctg has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.22 | CNBP_CCTG |
Louise Daugherty STR: CNBP_CCTG was added STR: CNBP_CCTG was added to Myotonia congenita. Sources: Expert list Mode of inheritance for STR: CNBP_CCTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: CNBP_CCTG were set to 18807109 Phenotypes for STR: CNBP_CCTG were set to Myotonic dystrophy 2, 602668 Review for STR: CNBP_CCTG was set to GREEN Added comment: STR added as part of the GMS. This STR is tested routinely using PCR-based methods in the NHS. Sources: Expert list |
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| Skeletal muscle channelopathy v0.21 | CNBP | Louise Daugherty Classified gene: CNBP as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.21 | CNBP | Louise Daugherty Added comment: Comment on list classification: demoted to Red, this review is for the STR entity and not the gene entity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.21 | CNBP | Louise Daugherty Gene: cnbp has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.21 | SLC2A1 | Louise Daugherty Classified gene: SLC2A1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.21 | SLC2A1 | Louise Daugherty Gene: slc2a1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.20 | SLC2A1 |
Louise Daugherty gene: SLC2A1 was added gene: SLC2A1 was added to Skeletal Muscle Channelopathies. Sources: Expert list Mode of inheritance for gene: SLC2A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SLC2A1 were set to 19630075; 26598494; 10980529 Phenotypes for gene: SLC2A1 were set to Epilepsy, idiopathic generalized, susceptibility to, 12, 614847; Can resemble skeletal muscle channelopathy; GLUT1 deficiency syndrome 1, infantile onset, severe, 606777 (recessive and dominant).; GLUT1 deficiency syndrome 2, childhood onset, 612126; myotonia; dystonia Review for gene: SLC2A1 was set to GREEN Added comment: added from review of the GMS myotonia congenita panel. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association. Sources: Expert list |
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| Skeletal Muscle Channelopathies v1.19 | ATP1A2 | Louise Daugherty Classified gene: ATP1A2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.19 | ATP1A2 | Louise Daugherty Added comment: Comment on list classification: Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.19 | ATP1A2 | Louise Daugherty Gene: atp1a2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.18 | ATP1A2 |
Louise Daugherty gene: ATP1A2 was added gene: ATP1A2 was added to Skeletal Muscle Channelopathies. Sources: Expert list Mode of inheritance for gene: ATP1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ATP1A2 were set to 30423015; 15286158; 18056581 Phenotypes for gene: ATP1A2 were set to Migraine, familial hemiplegic, 2, 602481; Alternating hemiplegia of childhood 1, 104290; Hypokalaemic periodic paralysis Review for gene: ATP1A2 was set to GREEN Added comment: added from review of the GMS myotonia congenita panel. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association. Sources: Expert list |
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| Skeletal muscle channelopathy v0.20 | ATP2A1 | Louise Daugherty Publications for gene: ATP2A1 were set to 8841193; 30423015; 15286158; 18056581 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.19 | ATP2A1 | Louise Daugherty Publications for gene: ATP2A1 were set to 8841193; 30423015; 15286158,18056581 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.18 | ATP2A1 | Louise Daugherty Added comment: Comment on publications: added additional publications to support Green rating. NB: SERCA1 is the previous gene symbol for ATP1A2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.18 | ATP2A1 | Louise Daugherty Publications for gene: ATP2A1 were set to 8841193 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.17 | KCNJ5 | Louise Daugherty commented on gene: KCNJ5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.17 | KCNQ2 | Louise Daugherty Classified gene: KCNQ2 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.17 | KCNQ2 | Louise Daugherty Added comment: Comment on list classification: Downgraded from Amber to Red. This gene was not submitted as part of the GMS on the Myotonia congenita panel, it is also noted by reviewer Fowzan Alkuraya that they do not think the evidence linking this gene to the intended phenotype for this panel i.e. muscle channelopathy is compelling | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.17 | KCNQ2 | Louise Daugherty Gene: kcnq2 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.16 | CACNB4 | Louise Daugherty Classified gene: CACNB4 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.16 | CACNB4 | Louise Daugherty Added comment: Comment on list classification: Downgraded from Amber to Red. This gene was not submitted as part of the GMS on the Myotonia congenita panel, it is also noted by reviewer Fowzan Alkuraya that they do not think the evidence linking this gene to the intended phenotype for this panel i.e. muscle channelopathy is compelling | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.16 | CACNB4 | Louise Daugherty Gene: cacnb4 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.15 | CACNA1A | Louise Daugherty Classified gene: CACNA1A as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.15 | CACNA1A | Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Since the original review in 2017 there has been more evidence to support variants of this gene resulting in a phenotype suitable for inclusion | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.15 | CACNA1A | Louise Daugherty Gene: cacna1a has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.14 | CACNA1A | Louise Daugherty Added comment: Comment on publications: added publications suggested by external reviwer on Myotonia congenita panel for GMS, new publication in particular new publication March 2018 https://www.ncbi.nlm.nih.gov/pubmed/?term=29442233 gives evidence to support variants of this gene resulting in a phenotype suitable for inclusion, there is also reference to a mouse model here : https://www.ncbi.nlm.nih.gov/pubmed/?term=28688851 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.14 | CACNA1A | Louise Daugherty Publications for gene: CACNA1A were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal Muscle Channelopathies v1.13 | CACNA1A | Louise Daugherty Mode of inheritance for gene: CACNA1A was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.56 | ANOS1 |
Eleanor Williams changed review comment from: PMID:9719154 reports overt renal failure in one adult with a contiguous deletion involving KAL1/ANOS1, and evidence of impaired renal function in a second adult with a clinical diagnosis of Kallmann syndrome. Both had unilateral renal agenesis. Note on MOI - PMID: 11297579 - Oliveira et al 2001 - report that "Genetically proven female carriers of KAL mutations in 3 families all had normal pubertal development, with regular menstrual cycles and normal olfaction". They also evaluated three families in which anosmic women gave birth to sons with KS, and none had any mutation in the coding sequence of the KAL gene. Therefore I think the MOI should be X-LINKED: hemizygous mutation in males, biallelic mutations in females as monoallelic females do not appear to present with the relevant phenotype.; to: PMID:9719154 Duke et al 1998 - reports overt renal failure in one adult with a contiguous deletion involving KAL1/ANOS1, and evidence of impaired renal function in a second adult with a clinical diagnosis of Kallmann syndrome. Both had unilateral renal agenesis. PMID: 17603054 - Georgopoulos et al 2007 - report renal dysgenesis in 2 out of 16 male KS patients. One had two missense mutations in the KAL1 gene, the other had deletion of exons 5–10 of the KAL1 gene and a complete deletion of the steroid sulphatase (STS) gene which accounts for the X-linked ichthyosis seen in that patient. PMID: 23533228 - Costa-Barbosa et al 2014 - report a cohort of 38 Kallman syndrome patients with rare variants in KAL1. 3/17 of them (where data was available) had renal agenesis. PMID: 25597551 - Xu et al 2015 - report 2 Chinese brothers with KS and X-linked ichthyosis. The phenotypes of the patients were characterised by bilateral cryptorchidism, unilateral renal agenesis in one patient but normal kidney development in another. The two affected siblings had the same novel deletion at Xp22.3 including exons 9-14 of KAL1 gene and entire STS gene. Note on MOI - PMID: 11297579 - Oliveira et al 2001 - report that "Genetically proven female carriers of KAL mutations in 3 families all had normal pubertal development, with regular menstrual cycles and normal olfaction". They also evaluated three families in which anosmic women gave birth to sons with KS, and none had any mutation in the coding sequence of the KAL gene. Therefore I think the MOI should be X-LINKED: hemizygous mutation in males, biallelic mutations in females as monoallelic females do not appear to present with the relevant phenotype. |
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| Unexplained young onset end-stage renal disease v0.56 | ANOS1 |
Eleanor Williams changed review comment from: Note on MOI - PMID: 11297579 - Oliveira et al 2001 - report that "Genetically proven female carriers of KAL mutations in 3 families all had normal pubertal development, with regular menstrual cycles and normal olfaction". They also evaluated three families in which anosmic women gave birth to sons with KS, and none had any mutation in the coding sequence of the KAL gene. ANOS1 was previously known as KAL1. Therefore I think the MOI should be X-LINKED: hemizygous mutation in males, biallelic mutations in females as monoallelic females do not appear to present with the relevant phenotype.; to: PMID:9719154 reports overt renal failure in one adult with a contiguous deletion involving KAL1/ANOS1, and evidence of impaired renal function in a second adult with a clinical diagnosis of Kallmann syndrome. Both had unilateral renal agenesis. Note on MOI - PMID: 11297579 - Oliveira et al 2001 - report that "Genetically proven female carriers of KAL mutations in 3 families all had normal pubertal development, with regular menstrual cycles and normal olfaction". They also evaluated three families in which anosmic women gave birth to sons with KS, and none had any mutation in the coding sequence of the KAL gene. Therefore I think the MOI should be X-LINKED: hemizygous mutation in males, biallelic mutations in females as monoallelic females do not appear to present with the relevant phenotype. |
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| Unexplained young onset end-stage renal disease v0.56 | APRT | Eleanor Williams changed review comment from: Comment on list classification: Although there are enough cases with variants in this gene associated with a relevant phenotype, rating this gene as Amber just now until it is decided whether patients with nephrolithiaisis should have this panel applied or the Nephrocalcinosis or nephrolithiasis panel.; to: Comment on list classification: Although there are enough cases with variants in this gene associated with a relevant phenotype, this gene has been rated as amber on this panel since patients present with nephrolithiaisis and it is likely more appropriate for them to have the Nephrocalcinosis or nephrolithiasis panel applied. The gene is green on the Nephrocalcinosis or nephrolithiasis panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.56 | APRT | Eleanor Williams Classified gene: APRT as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.56 | APRT | Eleanor Williams Added comment: Comment on list classification: Although there are enough cases with variants in this gene associated with a relevant phenotype, rating this gene as Amber just now until it is decided whether patients with nephrolithiaisis should have this panel applied or the Nephrocalcinosis or nephrolithiasis panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.56 | APRT | Eleanor Williams Gene: aprt has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.55 | APRT | Eleanor Williams Phenotypes for gene: APRT were changed from nterstitial nephritis; chronic kidney disease; end stage renal disease; nephrolithiaisis; Adenine phosphoribosyltransferase deficiency 614723 to interstitial nephritis; chronic kidney disease; end stage renal disease; nephrolithiaisis; Adenine phosphoribosyltransferase deficiency 614723 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.54 | APRT |
Eleanor Williams gene: APRT was added gene: APRT was added to Unexplained paediatric onset end-stage renal disease. Sources: Expert Review Mode of inheritance for gene: APRT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: APRT were set to 30355577; 30106368; 25307253; 22212387 Phenotypes for gene: APRT were set to nterstitial nephritis; chronic kidney disease; end stage renal disease; nephrolithiaisis; Adenine phosphoribosyltransferase deficiency 614723 Review for gene: APRT was set to AMBER Added comment: This gene was added to the 100,000 genomes project ' Unexplained kidney failure in young people' panel at the suggestion of external reviewer John Sayer. Associated with Adenine phosphoribosyltransferase deficiency (#614723)(AR) in OMIM with renal failure and Urolithiasis listed as clinical features. APRT is green on the Nephrocalcinosis or nephrolithiasis panel (https://panelapp.genomicsengland.co.uk/panels/149/gene/APRT/). > 3 cases reported in OMIM where variants in APRT are associated with Adenine phosphoribosyltransferase deficiency and a renal phenotype. Homozygous and compound heterozygous variants in APRT are associated with Adenine phosphoribosyltransferase deficiency and can lead to end-stage kidney disease if untreated. End-stage kidney disease can present under 50 years. Sources: Expert Review |
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| Unexplained young onset end-stage renal disease v0.53 | FAN1 | Eleanor Williams Classified gene: FAN1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.53 | FAN1 | Eleanor Williams Added comment: Comment on list classification: Sufficient cases to rate green for association with a relevant disease and presentation can be in young adults. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.53 | FAN1 | Eleanor Williams Gene: fan1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.52 | FAN1 |
Eleanor Williams gene: FAN1 was added gene: FAN1 was added to Unexplained paediatric onset end-stage renal disease. Sources: Expert Review Mode of inheritance for gene: FAN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAN1 were set to 22772369 Phenotypes for gene: FAN1 were set to interstitial nephritis; chronic kidney disease; Interstitial nephritis, karyomegalic 614817 Review for gene: FAN1 was set to GREEN Added comment: This gene was added to the 100,000 genomes project ' Unexplained kidney failure in young people' panel at the suggestion of external reviewer John Sayer. FAN1 associated with Interstitial nephritis, karyomegalic #614817 (AR) in OMIM. PMID: 22772369 - Zhou et al 2012 - 9 unrelated families with karyomegalic interstitial nephritis which can result in Chronic kidney disease. They identified 12 different homozygous or compound heterozygous mutations in the FAN1 gene. Eight of the 12 mutations resulted in a truncated protein. (Summary from OMIM). End-stage kidney failure ensued by a median age of 45 years in the 12 individuals with KIN and FAN1 mutations. Sufficient cases with likely disease causing mutations to rate this gene green. Sources: Expert Review |
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| Unexplained kidney failure in young people v1.82 | FAN1 | Eleanor Williams Phenotypes for gene: FAN1 were changed from interstitial nephritis; chronic kidney disease to interstitial nephritis; chronic kidney disease; Interstitial nephritis, karyomegalic 614817 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.81 | FAN1 | Eleanor Williams Classified gene: FAN1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.81 | FAN1 | Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team, rating this gene green as relevant phenotype with onset in 20s-30s is appropriate for this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.81 | FAN1 | Eleanor Williams Gene: fan1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.80 | APRT | Eleanor Williams commented on gene: APRT: After consultation with the Genomics England clinical team it has been decided to keep this gene amber on this panel. It is green on the Nephrocalcinosis or nephrolithiasis panel (https://panelapp.genomicsengland.co.uk/panels/149/) which is considered the more appropriate panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.16 | COL3A1 | Matthew Edwards changed review comment from: On CGGL Royal Brompton pneumothorax diagnostic panel. Pneumrpthorax is a minor diagnostic criteria in vEDS, therefore, although unlikely to be the presenting feature, COL3A1 appropriate for inclusion here.; to: On CGGL Royal Brompton pneumothorax diagnostic panel. Pneumothorax is a minor diagnostic criteria in vEDS, therefore, although unlikely to be the presenting feature, COL3A1 appropriate for inclusion here. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.50 | TRPM6 | Eleanor Williams changed review comment from: Comment on list classification: Demoting this gene from green to red. A PubMed search didn't find publications listing nephrocalicinosis/nephrolithiasis in association with this gene. Hypermagnesuria no hypomagnesemia is included on the eligibility statement for this disease.; to: Comment on list classification: Demoting this gene from green to red. A PubMed search didn't find publications listing nephrocalicinosis/nephrolithiasis in association with this gene. Hypermagnesuria not hypomagnesemia is included on the eligibility statement for this disease. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.50 | HNF4A | Eleanor Williams Phenotypes for gene: HNF4A were changed from to Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young, 616026 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.49 | HNF4A | Eleanor Williams Publications for gene: HNF4A were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.48 | SLC4A1 | Eleanor Williams Phenotypes for gene: SLC4A1 were changed from distal renal tubular acidosis to distal renal tubular acidosis; Renal tubular acidosis, distal, AD, 179800; Renal tubular acidosis, distal, AR 611590 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.16 | FBN1 | Louise Daugherty Phenotypes for gene: FBN1 were changed from Marfan syndrome to Marfan syndrome, 154700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.15 | FBN1 | Louise Daugherty Added comment: Comment on publications: added publication suggested by expert reviewer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.15 | FBN1 | Louise Daugherty Publications for gene: FBN1 were set to 12598898; 15161620; 11786720; 1864149; 2595640 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.14 | FLCN | Louise Daugherty Phenotypes for gene: FLCN were changed from Primary Spontaneous Pneumothorax; OMIM 173600; Birt-Hogg-Dube Syndrome; OMIM 135150; Birt-Hogg-Dube syndrome; Spontaneous Pneumothorax; Birt-Hogg-Dube Syndrome to Primary Spontaneous Pneumothorax, 173600; Birt-Hogg-Dube Syndrome, 135150; Birt-Hogg-Dube syndrome; Spontaneous Pneumothorax; Birt-Hogg-Dube Syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.13 | FLCN | Louise Daugherty Added comment: Comment on publications: added publication suggested by expert reviewer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.13 | FLCN | Louise Daugherty Publications for gene: FLCN were set to 21550484; 19483054; 15852235; 15805188; 15657874; 12204536; 26928018 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.12 | SERPINA1 | Louise Daugherty Added comment: Comment on phenotypes: added phenotype suggested by expert reviewer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.12 | SERPINA1 | Louise Daugherty Phenotypes for gene: SERPINA1 were changed from Emphysema due to AAT deficiency; Emphysema-cirrhosis, due to AAT deficiency to Emphysema due to AAT deficiency; Emphysema-cirrhosis, due to AAT deficiency; Emphysema/cirrhosis due to AAT deficiency, 613490 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.11 | TGFB2 | Louise Daugherty Added comment: Comment on phenotypes: added phenotype suggested by expert reviewer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.11 | TGFB2 | Louise Daugherty Phenotypes for gene: TGFB2 were changed from Loeys-Dietz syndrome; Pulmonary emphysema; Loeys-Dietz syndrome 4, 614816 to Loeys-Dietz syndrome; Pulmonary emphysema; Loeys-Dietz syndrome 4, 614816 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.10 | TGFB2 | Louise Daugherty Added comment: Comment on phenotypes: added phenotype suggested by expert reviewer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.10 | TGFB2 | Louise Daugherty Phenotypes for gene: TGFB2 were changed from Loeys-Dietz syndrome; Pulmonary emphysema to Loeys-Dietz syndrome; Pulmonary emphysema; Loeys-Dietz syndrome 4, 614816 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.9 | TGFB3 | Louise Daugherty Added comment: Comment on phenotypes: added phenotype suggested by expert reviewer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.9 | TGFB3 | Louise Daugherty Phenotypes for gene: TGFB3 were changed from Loeys-Dietz syndrome; Pulmonary emphysema; Loeys-Dietz syndrome 5, 615582 to Loeys-Dietz syndrome; Pulmonary emphysema; Loeys-Dietz syndrome 5, 615582 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.8 | TGFB3 | Louise Daugherty Phenotypes for gene: TGFB3 were changed from Loeys-Dietz syndrome; Pulmonary emphysema to Loeys-Dietz syndrome; Pulmonary emphysema; Loeys-Dietz syndrome 5, 615582 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.7 | TGFB3 | Louise Daugherty Added comment: Comment on publications: added publications suggested by expert reviewer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.7 | TGFB3 | Louise Daugherty Publications for gene: TGFB3 were set to 26493799; 15591413; 25006744; 23161884 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.6 | TGFBR1 | Louise Daugherty Added comment: Comment on publications: added publication suggested by expert reviewer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.6 | TGFBR1 | Louise Daugherty Publications for gene: TGFBR1 were set to 26493799; 15591413; 25006744; 23161884 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.5 | TGFBR1 | Louise Daugherty Added comment: Comment on phenotypes: added phenotype suggested by expert reviewer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.5 | TGFBR1 | Louise Daugherty Phenotypes for gene: TGFBR1 were changed from Loeys-Dietz syndrome; Pulmonary emphysema to Loeys-Dietz syndrome; Pulmonary emphysema; Loeys-Dietz syndrome 1, 609192 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.4 | TGFBR2 | Louise Daugherty Added comment: Comment on phenotypes: added phenotype suggested by expert reviewer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.4 | TGFBR2 | Louise Daugherty Phenotypes for gene: TGFBR2 were changed from Loeys-Dietz syndrome; Pulmonary emphysema to Loeys-Dietz syndrome; Pulmonary emphysema; Loeys-Dietz syndrome type 2, 610168 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.3 | TSC1 | Louise Daugherty Added comment: Comment on phenotypes: added phenotype suggested by expert reviewer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.3 | TSC1 | Louise Daugherty Phenotypes for gene: TSC1 were changed from Lymphangioleiomyomatosis (LAM); Tuberous sclerosis complex (TSC); Lymphangioleiomyomatosis to Lymphangioleiomyomatosis (LAM); Tuberous sclerosis complex (TSC); Lymphangioleiomyomatosis; Tuberous sclerosis 1, 191100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.2 | TSC2 | Louise Daugherty Phenotypes for gene: TSC2 were changed from Lymphangioleiomyomatosis (LAM); Tuberous sclerosis complex (TSC); Lymphangioleiomyomatosis to Lymphangioleiomyomatosis (LAM); Tuberous sclerosis complex (TSC); Lymphangioleiomyomatosis; Tuberous sclerosis 2, 613254 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.1 | SMAD3 | Louise Daugherty Added comment: Comment on phenotypes: added phenotype suggested by expert reviewer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.1 | SMAD3 | Louise Daugherty Phenotypes for gene: SMAD3 were changed from Loeys-Dietz syndrome; Pulmonary emphysema to Loeys-Dietz syndrome; Pulmonary emphysema; Loeys-Dietz syndrome type 3, 613795 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.405 | GOT2 | Rebecca Foulger commented on gene: GOT2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.405 | HNRNPR | Rebecca Foulger commented on gene: HNRNPR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.405 | HLCS | Rebecca Foulger Publications for gene: HLCS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.404 | HLCS | Rebecca Foulger Phenotypes for gene: HLCS were changed from to Holocarboxylase synthetase deficiency, 253270 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.403 | PLA2G6 | Rebecca Foulger Classified gene: PLA2G6 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.403 | PLA2G6 | Rebecca Foulger Added comment: Comment on list classification: Although PLA2G6 is Green on the 'Inborn errors of metabolism' panel, have added to the Epilepsy panel as Amber as unclear if seizures are a consistent feature. Requires clinical review (and review of the MOI in PMID:27513994) before promotion to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.403 | PLA2G6 | Rebecca Foulger Gene: pla2g6 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.402 | PLA2G6 | Rebecca Foulger Added comment: Comment on mode of inheritance: Selected 'BIALLELIC' inheritance to match the metabolism PanelApp panels (including Inborn errors of metabolism, V1.392), all OMIM disorders and both G2P disorders. However, PMID:27513994 report autosomal dominant inheritance for Familial cortical myoclonic tremor with epilepsy (FCMTE). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.402 | PLA2G6 | Rebecca Foulger Mode of inheritance for gene: PLA2G6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.401 | PLA2G6 | Rebecca Foulger commented on gene: PLA2G6: PMID:27513994 (Gao et al., 2016) report a family (41 members) which included 6 individuals affected with Familial cortical myoclonic tremor with epilepsy (FCMTE). All 6 individuals had tremors while 5 individuals had seizures. Genomic sequencing was performed on 3 affected and 2 unaffected individuals. A novel missense variant c.475C>T (p.A159T) in PLA2G6 with AD inheritance was identified in this family which segregated with the disease. Note that a variant in SNRNP200 gene also segregated with the disease but is within the untranslated region and the functional effect is unclear. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.401 | PLA2G6 | Rebecca Foulger commented on gene: PLA2G6: PMID:30772976. Ma et al., 2019 analyse a Chinese Han pedigree with seizures amongst the phenotype. Compound het variants in PLA2G6 were found (p.A80T and p.D331Y) (full English text not available). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.401 | PLA2G6 | Rebecca Foulger commented on gene: PLA2G6: PMID:30340910. Darling et al., 2019 investigated 16 patients from 13 families with PLA2G6-associated neurodegeneration (an autosomal recessive disorder). Epilepsy was observed in 8/16 patients (7 families, 2 patients had been previously reported, Table 1). All patients harboured missense, nonsense and frameshift variants in PLA2G6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.401 | PLA2G6 |
Rebecca Foulger gene: PLA2G6 was added gene: PLA2G6 was added to Genetic epilepsy syndromes. Sources: Literature,Other Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLA2G6 were set to 30340910; 27513994; 30772976 Phenotypes for gene: PLA2G6 were set to PLA2G6-associated neurodegeneration (PLAN); Familial cortical myoclonic tremor with epilepsy (FCMTE); Infantile neuroaxonal dystrophy 1, 256600; Neurodegeneration with brain iron accumulation 2B, 610217 Added comment: Added to epilepsy panel based on a Green rating on the 'Inborn errors of metabolism panel'- seizures are a reported feature of MIM:256600 and MIM:610217. Sources: Literature, Other |
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| Pneumothorax - familial v2.0 | SMAD3 | Matthew Edwards edited their review of gene: SMAD3: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.0 | SMAD3 | Matthew Edwards reviewed gene: SMAD3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: OMIM: 613795 Loeys-Dietz syndrome type 3; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.0 | TSC2 | Matthew Edwards reviewed gene: TSC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: OMIM 613254 Tuberous sclerosis-2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.400 | DNAJC5 | Rebecca Foulger Classified gene: DNAJC5 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.400 | DNAJC5 | Rebecca Foulger Added comment: Comment on list classification: Added to panel as a Green gene as seizures are a symptom of the metabolic disorder, and sufficient epilepsy cases from literature. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.400 | DNAJC5 | Rebecca Foulger Gene: dnajc5 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary ciliary disorders v1.22 | GAS2L2 | Eleanor Williams Classified gene: GAS2L2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary ciliary disorders v1.22 | GAS2L2 | Eleanor Williams Added comment: Comment on list classification: Demoting to Amber for now as this gene currently has no Ensembl IDs in PanelApp. Will promote to green again when this issue is resolved. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary ciliary disorders v1.22 | GAS2L2 | Eleanor Williams Gene: gas2l2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.399 | DNAJC5 | Rebecca Foulger commented on gene: DNAJC5: PMID:22235333: Velinov et al., 2012. The authors previously described the Parry family in the 1970s. All affected individuals from the family had a history of progressive seizure disorder. They identified a pLeu116del variant in DNAJC5 which segregated with the disease. 8 additional families were studied for this paper, with seizures amongst the phenotypes. In one affected individual, pLeu115Arg was identified (proband BD-319) who had seizures and gradual dementia beginning in the mid 30s. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.399 | DNAJC5 | Rebecca Foulger commented on gene: DNAJC5: PMID:29506599: Jarrett et al., 2018 report a family with Kufs disease in which the proband and 3/4 children presented with cognitive impariment, seizures and myoclonus. Genetic testing of all four children was positive for a c.346_348delCTC(p.L116del) variant in the DNAJC5 gene. EEG on the asymptomatic fourth child showed moderatley severe slowing. The proband's father was deceased but had a history of epileptic seizures. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.399 | DNAJC5 | Rebecca Foulger commented on gene: DNAJC5: PMID:22978711: Cadieux-Dion et al., 2013. report a p.L116del variant in DNAJC5 in two distinct American families, and a p.L115R variant in an additional family. All individuals showed generalized tonic-clonic seizures. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.399 | DNAJC5 |
Rebecca Foulger gene: DNAJC5 was added gene: DNAJC5 was added to Genetic epilepsy syndromes. Sources: Literature,Other Mode of inheritance for gene: DNAJC5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DNAJC5 were set to 22978711; 29506599; 22235333 Phenotypes for gene: DNAJC5 were set to Ceroid lipofuscinosis, neuronal, 4, Parry type, 162350; autosomal dominant Kufs disease; generalized tonic–clonic seizures Added comment: Added DNAJC5 to the Epilepsy panel based on a Green rating on the 'Inborn errors of metabolism' panel: seizures are listed as a symptom of MIM:162350 in OMIM. Sources: Literature, Other |
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| Pneumothorax - familial v2.0 | TSC1 | Matthew Edwards reviewed gene: TSC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23729718, 19318672; Phenotypes: OMIM 606690 Lymphangioleiomyomatosis (LAM), 191100 Tuberous sclerosis-1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.0 | TGFBR2 | Matthew Edwards reviewed gene: TGFBR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: OMIM: 610168 Loeys-Dietz syndrome type 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.0 | TGFBR1 | Matthew Edwards reviewed gene: TGFBR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16799921; Phenotypes: OMIM: 609192 Loeys-Dietz syndrome 1; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.0 | TGFB3 | Matthew Edwards reviewed gene: TGFB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24577266, 25835445; Phenotypes: OMIM: 615582 Loeys-Dietz syndrome 5; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.0 | TGFB2 | Matthew Edwards changed review comment from: On CGGL Royal Brompton panel. Several pathogenic variants (including CNVs) reported in LDS, with extensive segregation. Pneumothorax can be a feature of LDS, potentially repsenting feature, therefore appropriate for this apenl as well as FTAAD panel.; to: On CGGL Royal Brompton panel. Several pathogenic variants (including CNVs) reported in LDS, with extensive segregation. Pneumothorax can be a feature of LDS, potentially repsenting feature, therefore appropriate for this panel as well as FTAAD panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.0 | TGFB2 | Matthew Edwards reviewed gene: TGFB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26493799; Phenotypes: OMIM 614816 Loeys-Dietz syndrome (LDS) 4; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.0 | SERPINA1 | Matthew Edwards reviewed gene: SERPINA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22215832, 18619132; Phenotypes: OMIM 613490 Emphysema/cirrhosis due to AAT deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.0 | FLCN | Matthew Edwards reviewed gene: FLCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 15852235, 19483054, 12204536; Phenotypes: OMIM 173600 Pneumothorax, primary spontaneous, 135150 Birt-Hogg-Dube syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.0 | FBN1 | Matthew Edwards reviewed gene: FBN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 2595640, 12598898, 25765122; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.47 | CLCNKB | Eleanor Williams Added comment: Comment on mode of inheritance: In OMIM Autosomal recessive for Bartter syndrome, type 3 607364 and Digenic recessive for Bartter syndrome, type 4b, digenic 613090. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.47 | CLCNKB | Eleanor Williams Mode of inheritance for gene: CLCNKB was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.46 | CASR | Eleanor Williams Added comment: Comment on mode of pathogenicity: Expert review states that Hypocalcemia can be caused by a mutation that inappropriately activates the receptor | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.46 | CASR | Eleanor Williams Mode of pathogenicity for gene: CASR was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.45 | BSND | Eleanor Williams Added comment: Comment on mode of inheritance: AR in OMIM and Biallelic in Gene2Phenotype for Bartter syndrome, type 4a | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.45 | BSND | Eleanor Williams Mode of inheritance for gene: BSND was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.44 | ATP6V1B1 | Eleanor Williams Phenotypes for gene: ATP6V1B1 were changed from distal renal tubular acidosis to distal renal tubular acidosis; Renal tubular acidosis with deafness 267300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.43 | ATP6V0A4 | Eleanor Williams commented on gene: ATP6V0A4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.43 | PHEX | Eleanor Williams Classified gene: PHEX as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.43 | PHEX | Eleanor Williams Added comment: Comment on list classification: In light of expert review and consultation with the Genomics England clinical team it was decided to promote this gene from red to green. >3 cases reported with variants in this gene in patients with nephrocalicinosis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.43 | PHEX | Eleanor Williams Gene: phex has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.42 | PHEX | Eleanor Williams changed review comment from: Comment on mode of inheritance: Following XLD mode of inhertiance in OMIM, so changing to X-Linked: hemizyous mutation in males, monoallelic in females.; to: Comment on mode of inheritance: Following XLD mode of inhertiance in OMIM, so changing to X-Linked: hemizyous mutation in males, monoallelic in females. Monoallelic variants causing disease in females are reported e.g. PMID: 10439971 Filisetti et al 1999 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.42 | PHEX | Eleanor Williams Publications for gene: PHEX were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.41 | PHEX | Eleanor Williams Phenotypes for gene: PHEX were changed from to Hypophosphatemic rickets, X-linked dominant 307800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.40 | FAM20A | Eleanor Williams Classified gene: FAM20A as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.40 | FAM20A | Eleanor Williams Added comment: Comment on list classification: Upgrading from red to green. 3 independent cases where nephrocalcinosis is reported plus mouse knockout data showing a renal phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.40 | FAM20A | Eleanor Williams Gene: fam20a has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.39 | TRPM6 | Eleanor Williams Classified gene: TRPM6 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.39 | TRPM6 | Eleanor Williams Added comment: Comment on list classification: Demoting this gene from green to red. A PubMed search didn't find publications listing nephrocalicinosis/nephrolithiasis in association with this gene. Hypermagnesuria no hypomagnesemia is included on the eligibility statement for this disease. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.39 | TRPM6 | Eleanor Williams Gene: trpm6 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited pancreatic cancer v1.1 | RABL3 |
Ivone Leong gene: RABL3 was added gene: RABL3 was added to Inherited pancreatic cancer. Sources: Literature Mode of inheritance for gene: RABL3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RABL3 were set to 31406347 Phenotypes for gene: RABL3 were set to Hereditary pancreatic cancer Review for gene: RABL3 was set to AMBER Added comment: PMID: 31406347 describes a family with heterozygous variant in the RABL3 gene that causes a premature nonsense mutation. The family has multiple cases of pancreatic ductal adenocarcinoma. Sanger sequencing of the affected family showed significant co-segregation of the variant with cancer. Heterozygous knockdown of the rabl3 gene in zebrafish show increased susceptibility to cancer formation. Sources: Literature |
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| Silver Russell syndrome v1.9 | PLAG1 | Ivone Leong Classified gene: PLAG1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Silver Russell syndrome v1.9 | PLAG1 | Ivone Leong Added comment: Comment on list classification: Promoted from Red to Green. This gene is a Green gene on the Growth failure in early childhood panel (code 473, v1.3), which has been signed off by the GMS Endocrinology specialist group (31/07/2019). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Silver Russell syndrome v1.9 | PLAG1 | Ivone Leong Gene: plag1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Silver Russell syndrome v1.8 | PLAG1 | Ivone Leong Phenotypes for gene: PLAG1 were changed from to SRS; Silver-Russell syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Silver Russell syndrome v1.7 | PLAG1 |
Ivone Leong gene: PLAG1 was added gene: PLAG1 was added to Silver Russell syndrome. Sources: Expert Review Mode of inheritance for gene: PLAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PLAG1 were set to 28796236 |
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| Silver Russell syndrome v1.6 | HMGA2 | Ivone Leong Classified gene: HMGA2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Silver Russell syndrome v1.6 | HMGA2 | Ivone Leong Gene: hmga2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Silver Russell syndrome v1.5 | HMGA2 |
Ivone Leong gene: HMGA2 was added gene: HMGA2 was added to Silver Russell syndrome. Sources: Expert Review Mode of inheritance for gene: HMGA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HMGA2 were set to 29655892 Phenotypes for gene: HMGA2 were set to SRS; Silver-Russell syndrome Review for gene: HMGA2 was set to GREEN Added comment: This is a Green gene on the Growth failure in early childhood panel (code 473, v1.3), which has been signed off by the GMS Endocrinology specialist group (31/07/2019). Sources: Expert Review |
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| Silver Russell syndrome v1.4 | IGF2 | Ivone Leong Classified gene: IGF2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Silver Russell syndrome v1.4 | IGF2 | Ivone Leong Added comment: Comment on list classification: Promoted from Red to Green as this gene is a Green gene on the Growth failure in early childhood panel (code 473, v1.3), which has been signed off by the GMS Endocrinology specialist group (31/07/2019). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Silver Russell syndrome v1.4 | IGF2 | Ivone Leong Gene: igf2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.3 | TMEM132E | Eleanor Williams Tag watchlist tag was added to gene: TMEM132E. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.80 | FAN1 | Eleanor Williams Classified gene: FAN1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.80 | FAN1 | Eleanor Williams Added comment: Comment on list classification: Downgrading from green to amber while consulting with the Genomics England clinical team as to the suitability of this gene as the age of onset for renal disease is from 30 year old onwards. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.80 | FAN1 | Eleanor Williams Gene: fan1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.79 | APRT | Eleanor Williams Classified gene: APRT as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.79 | APRT | Eleanor Williams Added comment: Comment on list classification: Downgrading from Green to Amber as presence of Nephrolithiasis is part of the exclusion criteria. Will consult with the Genomics England clinical team as to whether this gene should be included on this panel or not. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.79 | APRT | Eleanor Williams Gene: aprt has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.78 | FAN1 |
Eleanor Williams changed review comment from: FAN1 associated with Interstitial nephritis, karyomegalic #614817 (AR) in OMIM. PMID: 22772369 - Zhou et al 2012 - 9 unrelated families with karyomegalic interstitial nephritis which can result in Chronic kidney disease. They identified 12 different homozygous or compound heterozygous mutations in the FAN1 gene. Eight of the 12 mutations resulted in a truncated protein. (Summary from OMIM). Sufficient cases with likely disease causing mutations to rate this gene green. ; to: FAN1 associated with Interstitial nephritis, karyomegalic #614817 (AR) in OMIM. PMID: 22772369 - Zhou et al 2012 - 9 unrelated families with karyomegalic interstitial nephritis which can result in Chronic kidney disease. They identified 12 different homozygous or compound heterozygous mutations in the FAN1 gene. Eight of the 12 mutations resulted in a truncated protein. (Summary from OMIM). End-stage kidney failure ensued by a median age of 45 years in the 12 individuals with KIN and FAN1 mutations. Sufficient cases with likely disease causing mutations to rate this gene green. |
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| Primary ciliary disorders v1.21 | GAS2L2 | Eleanor Williams Classified gene: GAS2L2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary ciliary disorders v1.21 | GAS2L2 | Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team it was decided to change the rating of this gene from Amber to Green based on the additional green expert review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary ciliary disorders v1.21 | GAS2L2 | Eleanor Williams Gene: gas2l2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary ciliary disorders v1.20 | GAS2L2 | Eleanor Williams Phenotypes for gene: GAS2L2 were changed from Primary ciliary dyskinesia to Primary ciliary dyskinesia; ?Ciliary dyskinesia, primary, 41 618449 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.3 | TMEM132E | Eleanor Williams edited their review of gene: TMEM132E: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monogenic hearing loss v2.3 | TMEM132E |
Eleanor Williams gene: TMEM132E was added gene: TMEM132E was added to Hearing loss. Sources: Literature Mode of inheritance for gene: TMEM132E was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM132E were set to 25331638; 31656313 Phenotypes for gene: TMEM132E were set to Nonsyndromic Hearing Loss Review for gene: TMEM132E was set to RED Added comment: Two publications support the addition of this gene to the panel: PMID: 25331638 - Li et al 2015 - report two siblings with prelingual, bilateral, severe to profound sensorineural hearing loss in a consanguineous Chinese family. Whole‐exome sequencing revealed a homozygous missense mutation c.1259G>A (rs139895222), p.Arg420Gln, in TMEM132E that cosegregates with deafness in the family. The parents and a brother were heterozygous. The 1259A allele was not found in 500 ethnically matched controls. Immunofluorescence staining of the Organ of Corti showed Tmem132e highly expressed in murine inner hair cells and knockdown of the tmem132e ortholog in zebrafish affected the mechanotransduction of hair cells. Wild‐type human TMEM132E mRNA, but not the mRNA carrying the c.1259G>A mutation rescued the Tmem132e knockdown phenotype. PMID: 31656313 - Liaqat et al 2019 - a family of Pakistani origin with prelingual profound sensorineural hearing impairment displaying AR mode of inheritance was investigated via exome and Sanger sequencing. Compound heterozygous variants c.382G>T: p.(Ala128Ser) and c.2204C>T: p.(Pro735Leu) in TMEM132E were observed in affected but not in unaffected family members. Sources: Literature |
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| Unexplained kidney failure in young people v1.78 | APRT | Eleanor Williams Publications for gene: APRT were set to 30355577 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.77 | APRT | Eleanor Williams Classified gene: APRT as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.77 | APRT | Eleanor Williams Added comment: Comment on list classification: There are more than 3 cases where homozygous or compound heterozygous variants in APRT have been reported in patients with Adenine phosphoribosyltransferase deficiency. PMID: 30106368 and PMID: 25307253 report cases in which end-stage renal disease has been observed under the age of 50. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.77 | APRT | Eleanor Williams Gene: aprt has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.76 | APRT | Eleanor Williams Phenotypes for gene: APRT were changed from interstitial nephritis; chronic kidney disease; end stage renal disease; nephrolithiaisis to interstitial nephritis; chronic kidney disease; end stage renal disease; nephrolithiaisis; Adenine phosphoribosyltransferase deficiency 614723 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.75 | APRT | Eleanor Williams commented on gene: APRT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy v1.335 | Louise Daugherty List of related panels changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease; R78 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v2.0 | Louise Daugherty promoted panel to version 2.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v1.19 | Louise Daugherty Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v1.18 | SMAD3 | Louise Daugherty commented on gene: SMAD3: October 2019: Gene flagged up for further discussion by Respiratory Test Group regarding the inclusion of genes associated with Loeys-Dietz syndrome and classical EDS. However, no additional feedback was received, so gene will not be upgraded to Green as inclusion on this panel remains unclear. COL5A1, SMAD2 and SMAD3 are rated Green on the R101 Ehlers Danlos syndromes panel https://panelapp.genomicsengland.co.uk/panels/53/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v1.18 | SMAD2 | Louise Daugherty commented on gene: SMAD2: October 2019: Gene flagged up for further discussion by Respiratory Test Group regarding the inclusion of genes associated with Loeys-Dietz syndrome and classical EDS. However, no additional feedback was received, so gene will not be upgraded to Green as inclusion on this panel remains unclear. COL5A1, SMAD2 and SMAD3 are rated Green on the R101 Ehlers Danlos syndromes panel https://panelapp.genomicsengland.co.uk/panels/53/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pneumothorax - familial v1.18 | COL5A1 | Louise Daugherty commented on gene: COL5A1: October 2019: Gene flagged up for further discussion by Respiratory Test Group regarding the inclusion of genes associated with Loeys-Dietz syndrome and classical EDS. However, no additional feedback was received, so gene will not be upgraded to Green as inclusion on this panel remains unclear. COL5A1, SMAD2 and SMAD3 are rated Green on the R101 Ehlers Danlos syndromes panel https://panelapp.genomicsengland.co.uk/panels/53/ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset hereditary spastic paraplegia v1.1 | L1CAM | Louise Daugherty Added comment: Comment on mode of inheritance: Changed MOI due to upload of review MOI "X-LINKED recessive: hemizygous mutation in males, biallelic mutations in females" in inclusion of 'recessive' would result in an error with tiering, so has been corrected to 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset hereditary spastic paraplegia v1.1 | L1CAM | Louise Daugherty Mode of inheritance for gene: L1CAM was changed from X-LINKED recessive: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.148 | CIC | Rebecca Foulger changed review comment from: Original DDG2P rating: possible. DDG2P mode of pathogenicity: uncertain ; to: Original DDG2P rating for CAPICUA, DROSOPHILA, HOMOLOG OF: possible. DDG2P mode of pathogenicity: uncertain. Allelic requirement: monoallelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.148 | CIC | Rebecca Foulger changed review comment from: Comment on mode of pathogenicity: Changed MOP to default LOF to match current Mutation consequence in Gene2Phenotype of 'Loss of Function'.; to: Comment on mode of pathogenicity: Changed MOP to default LOF to match Gene2Phenotype update: current Mutation consequence in Gene2Phenotype is 'Loss of Function'. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.148 | CIC | Rebecca Foulger Added comment: Comment on mode of pathogenicity: Changed MOP to default LOF to match current Mutation consequence in Gene2Phenotype of 'Loss of Function'. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.148 | CIC | Rebecca Foulger Mode of pathogenicity for gene: CIC was changed from Other - please provide details in the comments to None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.147 | CIC | Rebecca Foulger Classified gene: CIC as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.147 | CIC | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber following a change in G2P Disease confidence from possible to probable for 'CAPICUA, DROSOPHILA, HOMOLOG OF'. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.147 | CIC | Rebecca Foulger Gene: cic has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.146 | FAM58A | Rebecca Foulger commented on gene: FAM58A: The Gene2Phenotype allelic requirement for STAR SYNDROME has been updated to x-linked dominant, to match the recent update in PanelApp. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.146 | AMER1 | Rebecca Foulger commented on gene: AMER1: The Gene2Phenotype allelic requirement for OSTEOPATHIA STRIATA WITH CRANIAL SCLEROSIS has been updated to x-linked dominant, to match the recent update in PanelApp. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.146 | ACTL6B | Rebecca Foulger Added comment: Comment on phenotypes: Removed 'Unspecified Neurodevelopmental Disorder' from phenotypes to match G2P update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.146 | ACTL6B | Rebecca Foulger Phenotypes for gene: ACTL6B were changed from Unspecified Neurodevelopmental Disorder; EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE 618468; INTELLECTUAL DEVELOPMENTAL DISORDER WITH SEVERE SPEECH AND AMBULATION DEFECTS 618470 to EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE 618468; INTELLECTUAL DEVELOPMENTAL DISORDER WITH SEVERE SPEECH AND AMBULATION DEFECTS 618470 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.40 | ANOS1 | Eleanor Williams Added comment: Comment on mode of inheritance: Updating the MOI to X-LINKED: hemizygous mutation in males, biallelic mutations in females. This MOI has proposed by an expert reviewer and agrees with that found in OMIM. PMID: 15001591 - reports only male cases with ANOS1 variants, with female carriers, PMID: 11297579 - reports male cases and states that obligate female carriers in families with KAL mutations have no discernible phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.40 | ANOS1 | Eleanor Williams Mode of inheritance for gene: ANOS1 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.75 | ANOS1 | Eleanor Williams changed review comment from: Comment on mode of inheritance: Updating the MOI to X-LINKED: hemizygous mutation in males, biallelic mutations in females. This MOI has proposed by 2 reviewers and agrees with that found in OMIM. PMID: 15001591 - reports only male cases with ANOS1 variants, with female carriers, PMID: 11297579 - reports male cases and states that obligate female carriers in families with KAL mutations have no discernible phenotype.; to: Comment on mode of inheritance: Updating the MOI to X-LINKED: hemizygous mutation in males, biallelic mutations in females. This MOI has proposed by 1reviewer and agrees with that found in OMIM. PMID: 15001591 - reports only male cases with ANOS1 variants, with female carriers, PMID: 11297579 - reports male cases and states that obligate female carriers in families with KAL mutations have no discernible phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.75 | ANOS1 | Eleanor Williams Added comment: Comment on mode of inheritance: Updating the MOI to X-LINKED: hemizygous mutation in males, biallelic mutations in females. This MOI has proposed by 2 reviewers and agrees with that found in OMIM. PMID: 15001591 - reports only male cases with ANOS1 variants, with female carriers, PMID: 11297579 - reports male cases and states that obligate female carriers in families with KAL mutations have no discernible phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained kidney failure in young people v1.75 | ANOS1 | Eleanor Williams Mode of inheritance for gene: ANOS1 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.145 | SLC35A2 | Rebecca Foulger Phenotypes for gene: SLC35A2 were changed from CONGENITAL DISORDER OF GLYCOSYLATION to Epileptic Encephalopathy due to congenital disorder of glycosylation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.144 | SLC35A2 | Rebecca Foulger Publications for gene: SLC35A2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Respiratory ciliopathies including non-CF bronchiectasis v1.0 | FOXJ1 |
Hannah Mitchison gene: FOXJ1 was added gene: FOXJ1 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: Literature Mode of inheritance for gene: FOXJ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FOXJ1 were set to PMID: 31630787 Phenotypes for gene: FOXJ1 were set to Motile ciliopathy; situs inversus, hydrocephalus Penetrance for gene: FOXJ1 were set to Complete Mode of pathogenicity for gene: FOXJ1 was set to Other Review for gene: FOXJ1 was set to AMBER Added comment: Wallmeier et al 2019 report the first known cause of autosomal dominant 'PCD' - referred to here more as a motile ciliopathy, than strictly PCD, because there are reduced cilia numbers but no structural changes in the cilia axonemes which are typical for diagnosing PCD. The reported mutations are associated in this sole paper with haploinsufficiency. Wallmeier et al report FOXJ1 mutations in 6 unrelated patients - all were heterozygous, single de novo variants. Sources: Literature |
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| Surfactant deficiency v1.0 | Louise Daugherty promoted panel to version 1.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Surfactant deficiency v0.29 | Louise Daugherty Panel types changed to GMS Rare Disease; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Respiratory ciliopathies including non-CF bronchiectasis v1.0 | Louise Daugherty promoted panel to version 1.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Respiratory ciliopathies including non-CF bronchiectasis v0.157 | Louise Daugherty Panel types changed to GMS Rare Disease; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v1.0 | Louise Daugherty promoted panel to version 1.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and platelet disorders v0.79 | Louise Daugherty Panel types changed to GMS Rare Disease; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypogonadotropic hypogonadism v1.27 | ANOS1 | Eleanor Williams changed review comment from: Comment on mode of inheritance: Updating the mode of inheritance from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females. This gene is not in the pseudoautosomal region of the X chromosome.; to: Comment on mode of inheritance: Updating the mode of inheritance from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females. This gene is not in the pseudoautosomal region of the X chromosome. Mode of inhertiance in OMIM is XLR for Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1) and several papers support this e.g. PMID: 15001591 - reports only male cases with ANOS1 variants, with female carriers, PMID: 11297579 - reports male cases and states that obligate female carriers in families with KAL mutations have no discernible phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypogonadotropic hypogonadism (GMS) v1.1 | ANOS1 | Ivone Leong Added comment: Comment on mode of inheritance: MOI was corrected. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypogonadotropic hypogonadism (GMS) v1.1 | ANOS1 | Ivone Leong Mode of inheritance for gene: ANOS1 was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.392 | DNM2 | Catherine Snow Mode of inheritance for gene: DNM2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.411 | SETX | Catherine Snow Classified gene: SETX as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.411 | SETX | Catherine Snow Gene: setx has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.410 | SETX | Catherine Snow reviewed gene: SETX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyotrophic lateral sclerosis 4, juvenile, 602433, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, 606002; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypogonadotropic hypogonadism v1.27 | ANOS1 | Eleanor Williams Added comment: Comment on mode of inheritance: Updating the mode of inheritance from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females. This gene is not in the pseudoautosomal region of the X chromosome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypogonadotropic hypogonadism v1.27 | ANOS1 | Eleanor Williams Mode of inheritance for gene: ANOS1 was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.391 | SETX | Catherine Snow Classified gene: SETX as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.391 | SETX | Catherine Snow Gene: setx has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | VWF | Louise Daugherty Source Expert Review Red was added to VWF. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | VPS13B | Louise Daugherty Source Expert Review Red was added to VPS13B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | TUBB1 |
Louise Daugherty Source Expert Review Amber was added to TUBB1. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | TCN2 |
Louise Daugherty Source Expert Review Amber was added to TCN2. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | STK4 | Louise Daugherty Source Expert Review Red was added to STK4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | STIM1 |
Louise Daugherty Source Expert Review Amber was added to STIM1. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | SRC |
Louise Daugherty Source Expert Review Green was added to SRC. Rating Changed from Red List (low evidence) to Green List (high evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | SLFN14 |
Louise Daugherty Source Expert Review Amber was added to SLFN14. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | RUNX1 |
Louise Daugherty Source Expert Review Amber was added to RUNX1. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | RNU4ATAC | Louise Daugherty Source Expert Review Red was added to RNU4ATAC. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | RBM8A |
Louise Daugherty Source Expert Review Red was added to RBM8A. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | PTPN11 | Louise Daugherty Source Expert Review Red was added to PTPN11. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | PSMB8 | Louise Daugherty Source Expert Review Red was added to PSMB8. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | NBEAL2 |
Louise Daugherty Source Expert Review Amber was added to NBEAL2. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | MYH9 |
Louise Daugherty Source Expert Review Amber was added to MYH9. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | MTHFD1 | Louise Daugherty Source Expert Review Red was added to MTHFD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | MSN | Louise Daugherty Source Expert Review Red was added to MSN. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | MPIG6B |
Louise Daugherty Source Expert Review Red was added to MPIG6B. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | LYST | Louise Daugherty Source Expert Review Red was added to LYST. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | LAMTOR2 | Louise Daugherty Source Expert Review Red was added to LAMTOR2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | KDSR | Louise Daugherty Source Expert Review Red was added to KDSR. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | ITGB3 | Louise Daugherty Source Expert Review Red was added to ITGB3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | ITGA2B | Louise Daugherty Source Expert Review Red was added to ITGA2B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | HTRA2 | Louise Daugherty Source Expert Review Red was added to HTRA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | HOXA11 |
Louise Daugherty Source Expert Review Red was added to HOXA11. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | GP9 |
Louise Daugherty Source Expert Review Amber was added to GP9. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | GP1BB |
Louise Daugherty Source Expert Review Amber was added to GP1BB. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | GP1BA |
Louise Daugherty Source Expert Review Amber was added to GP1BA. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | GNE | Louise Daugherty Source Expert Review Red was added to GNE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | GINS1 | Louise Daugherty Source Expert Review Red was added to GINS1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | FLNA | Louise Daugherty Source Expert Review Red was added to FLNA. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | FLI1 |
Louise Daugherty Source Expert Review Amber was added to FLI1. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | DIAPH1 | Louise Daugherty Source Expert Review Red was added to DIAPH1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | CLPB | Louise Daugherty Source Expert Review Red was added to CLPB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | CDC42 | Louise Daugherty Source Expert Review Red was added to CDC42. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | CD40LG | Louise Daugherty Source Expert Review Red was added to CD40LG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | CD40 | Louise Daugherty Source Expert Review Red was added to CD40. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | ARPC1B | Louise Daugherty Source Expert Review Red was added to ARPC1B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | AP3B1 |
Louise Daugherty Source Expert Review Amber was added to AP3B1. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | ADAMTS13 |
Louise Daugherty Source Expert Review Amber was added to ADAMTS13. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | ACTN1 |
Louise Daugherty Source Expert Review Amber was added to ACTN1. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | ACTB | Louise Daugherty Source Expert Review Red was added to ACTB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.136 | ABCG8 |
Louise Daugherty Source Expert Review Amber was added to ABCG8. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.136 | ABCG5 |
Louise Daugherty Source Expert Review Amber was added to ABCG5. Rating Changed from Red List (low evidence) to Amber List (moderate evidence) |
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| Cytopenia - NOT Fanconi anaemia v0.135 | WAS | Louise Daugherty edited their review of gene: WAS: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there is enough evidence to rate this gene Green. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Wiskott-Aldrich syndrome, can present as neonatal thrombocytopenia; North West GLH: no comment submitted; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | VWF | Louise Daugherty reviewed gene: VWF: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | VPS13B | Louise Daugherty reviewed gene: VPS13B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | TUBB1 | Louise Daugherty commented on gene: TUBB1: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there was only enough evidence to rate this gene Amber. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Macrothrombocytopenia, beta-tubulin 1 related; North West GLH: Not isolated thrombocytopenia; Yorkshire and North East GLH: no comment submitted;London South GLH: no comment submitted. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | THPO | Louise Daugherty edited their review of gene: THPO: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there is enough evidence to rate this gene Green. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH:Thrombocytopenia progressing to trilineage bone marrow failure; North West GLH: no comment submitted; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | TCN2 | Louise Daugherty reviewed gene: TCN2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | STK4 | Louise Daugherty reviewed gene: STK4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | STIM1 | Louise Daugherty commented on gene: STIM1: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there was only enough evidence to rate this gene Amber. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Stormorken syndrome (York platelet syndrome); North West GLH: Syndromic, not isolated thrombocytopenia; Yorkshire and North East GLH: no commetn submitted; London South GLH: no comment submitted. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | SRC | Louise Daugherty reviewed gene: SRC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | SMARCAL1 | Louise Daugherty edited their review of gene: SMARCAL1: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agree to rate this gene Red on this panel. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Multisystem disorder, skeletal defects seem to be consistently present, has not been associated with a cytopenia as presenting symptom; North West GLH:Syndromic, not isolated thrombocytopenia; Yorkshire and North East GLH:no comment submitted; London South GLH: no comment submitted; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | SLFN14 | Louise Daugherty reviewed gene: SLFN14: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | SLC37A4 | Louise Daugherty edited their review of gene: SLC37A4: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agree to rate this gene Red on this panel. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Glycogen storage disorders - other syndromic features (eg hypoglycaemia and splenomegaly) unlikely to present as neutropenia; North West GLH: Syndromic features, neutropenia, not isolated Thrombocytopenia; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | RUNX1 | Louise Daugherty commented on gene: RUNX1: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there was only enough evidence to rate this gene Amber. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Familial platelet disorder with predisposition to AML, typically presents with mild to moderate thrombocytopenia (normal sized platelets); North West GLH: Syndromic, not isolated thrombocytopenia; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | RNU4ATAC | Louise Daugherty reviewed gene: RNU4ATAC: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | RBM8A | Louise Daugherty edited their review of gene: RBM8A: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agree to rate this gene Red on this panel. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Thrombocytopenia-absent radius syndrome (TAR); Thrombocytopenia is variable but skeletal abnormalities are always present so I would class red; however already agreed as Amber in July Update October: RBM8A is green on R90 (bleeding & platelet disorders panel), so its covered. Considering this, Id favour Red on R91 for consistency with other syndromic thrombocytopenia associated genes that weve considered for this panel; North West GLH: Syndromic, not isolated thrombocytopenia; Yorkshire and North East GLH: no comment submitted ;London South GLH: no comment submitted.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | PTPN11 | Louise Daugherty reviewed gene: PTPN11: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | PSMB8 | Louise Daugherty reviewed gene: PSMB8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | NBEAL2 | Louise Daugherty commented on gene: NBEAL2: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there was only enough evidence to rate this gene Amber. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Gray platelet syndrome; associated with low platelet count; North West GLH: Not isolated thrombocytopenia; Yorkshire and North East GLH:no comment submitted; London South GLH: no comment submitted. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | MYH9 | Louise Daugherty commented on gene: MYH9: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there was only enough evidence to rate this gene Amber. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: May-Hegglin and other MYH9 disorders (macrothrombocytopenia plus other syndromic features); North West GLH: Syndromic, not isolated thrombocytopenia; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | MTHFD1 | Louise Daugherty reviewed gene: MTHFD1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | MSN | Louise Daugherty reviewed gene: MSN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | MPL | Louise Daugherty edited their review of gene: MPL: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there is enough evidence to rate this gene Green. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Congenital amegakaryocytic thrombocytopenia (CAMT) presents with isolated thrombocytopenia in infancy and developing into a pancytopenia in later childhood); North West GLH: no comment submitted; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | MPIG6B | Louise Daugherty edited their review of gene: MPIG6B: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agree to rate this gene Red on this panel. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Typically Thrombocytopenia, anemia and myelofibrosis (myelofibrosis is a distinct phenotype that is not targeted by this panel) - but one case of child presenting with pancytopenia; North West GLH: Syndromic, not isolated thrombocytopenia; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | MECOM | Louise Daugherty edited their review of gene: MECOM: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there is enough evidence to rate this gene Green. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Clinical spectrum ranged from isolated radioulnar synostosis with no or mild hematological involvement to severe bone marrow failure without obvious skeletal abnormality. Germeshausen 2018;North West GLH: no comment submitted; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | LYST | Louise Daugherty reviewed gene: LYST: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | LAMTOR2 | Louise Daugherty reviewed gene: LAMTOR2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | KDSR | Louise Daugherty reviewed gene: KDSR: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | ITGB3 | Louise Daugherty reviewed gene: ITGB3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | ITGA2B | Louise Daugherty reviewed gene: ITGA2B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | HTRA2 | Louise Daugherty reviewed gene: HTRA2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | HOXA11 | Louise Daugherty edited their review of gene: HOXA11: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agree to rate this gene Red on this panel. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Amegakaryocytic thrombocytopenia with radioulnar synostosis; so far has always been described in combination with obvious skeletal defect; North West GLH: Syndromic, not isolated thrombocytopenia; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | GP9 | Louise Daugherty reviewed gene: GP9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | GP1BB | Louise Daugherty reviewed gene: GP1BB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | GP1BA | Louise Daugherty commented on gene: GP1BA: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there was only enough evidence to rate this gene Amber. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Mild macrothrombocytopenia; North West GLH: Platelet type VWD, mild thrombocytopenia; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | GNE | Louise Daugherty reviewed gene: GNE: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | GINS1 | Louise Daugherty reviewed gene: GINS1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | GFI1 | Louise Daugherty edited their review of gene: GFI1: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there is enough evidence to rate this gene Green. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Platelet type bleeding disorder 17; Severe congenital neutropenia 2; North West GLH: no comment submitted; Yorkshire and North East GLH: only 2 changes on HGMD neutropenia; London South GLH: no comment submitted. ; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | GATA1 | Louise Daugherty edited their review of gene: GATA1: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there is enough evidence to rate this gene Green. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: X-linked thrombocytopenia with dyserythropoiesis; North West GLH: no comment submitted; Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted. ; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | FYB1 | Louise Daugherty edited their review of gene: FYB1: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there is enough evidence to rate this gene Green. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Thrombocytopenia 3; North West GLH: no comment submitted; Yorkshire and North East GLH: Rare (2cases); London South GLH: no comment submitted.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | FLNA | Louise Daugherty reviewed gene: FLNA: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | FLI1 | Louise Daugherty reviewed gene: FLI1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | ETV6 | Louise Daugherty edited their review of gene: ETV6: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there is enough evidence to rate this gene Green. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Thrombocytopenia and susceptibility to cancer; North West GLH: no comment submitted; Yorkshire and North East GLH:mainly somatic AML and some thrombocytopenia; London South GLH: no comment submitted.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | DIAPH1 | Louise Daugherty reviewed gene: DIAPH1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | CYCS | Louise Daugherty edited their review of gene: CYCS: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there is enough evidence to rate this gene Green. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Autosomal dominant thrombocytopenia 4; North West GLH: no comment submitted; Yorkshire and North East GLH: rare (4 cases); London South GLH: no comment submitted.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | CLPB | Louise Daugherty reviewed gene: CLPB: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | CDC42 | Louise Daugherty reviewed gene: CDC42: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | CD40LG | Louise Daugherty reviewed gene: CD40LG: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | CD40 | Louise Daugherty reviewed gene: CD40: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | ARPC1B | Louise Daugherty reviewed gene: ARPC1B: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | AP3B1 | Louise Daugherty reviewed gene: AP3B1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | ANKRD26 | Louise Daugherty edited their review of gene: ANKRD26: Added comment: Gene reviewed due to Haematology Specialist Test Group considering the inclusion of relevant neutropenia thrombocytopenia genes. The Specialist Test Group 21st October 2019 (consisting of 4 centres: WWMGLH, NWGLH, YNEGLH, LSGLH) all agreed that there is enough evidence to rate this gene Green. Additional comments from Haematology Specialist Test Group (Copy of Extra genes R91_consensus_v2.xlsx) 21st October 2019. Wessex and West Midlands GLH: Autosomal dominant thrombocytopenia 2; North West GLH: TTP and Upshaw-Schulman syndrome (recessive TTP); Yorkshire and North East GLH: no comment submitted; London South GLH: no comment submitted. ; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | ADAMTS13 | Louise Daugherty reviewed gene: ADAMTS13: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | ACTN1 | Louise Daugherty reviewed gene: ACTN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | ACTB | Louise Daugherty reviewed gene: ACTB: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | ABCG8 | Louise Daugherty reviewed gene: ABCG8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.135 | ABCG5 | Louise Daugherty reviewed gene: ABCG5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | WAS | Louise Daugherty Source Expert review Green was added to WAS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | VWF | Louise Daugherty Source Expert review Red was added to VWF. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | VPS13B | Louise Daugherty Source Expert review Red was added to VPS13B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | TUBB1 | Louise Daugherty Source Expert review Amber was added to TUBB1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | THPO | Louise Daugherty Source Expert review Green was added to THPO. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | TCN2 | Louise Daugherty Source Expert review Amber was added to TCN2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | STK4 | Louise Daugherty Source Expert review Red was added to STK4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | STIM1 | Louise Daugherty Source Expert review Amber was added to STIM1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | SRC | Louise Daugherty Source Expert review Green was added to SRC. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | SMARCAL1 | Louise Daugherty Source Expert review Red was added to SMARCAL1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | SLFN14 | Louise Daugherty Source Expert review Amber was added to SLFN14. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | SLC37A4 | Louise Daugherty Source Expert review Red was added to SLC37A4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | RUNX1 | Louise Daugherty Source Expert review Amber was added to RUNX1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | RNU4ATAC | Louise Daugherty Source Expert review Red was added to RNU4ATAC. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | RBM8A | Louise Daugherty Source Expert review Red was added to RBM8A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | PTPN11 | Louise Daugherty Source Expert review Red was added to PTPN11. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | PSMB8 | Louise Daugherty Source Expert review Red was added to PSMB8. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | NBEAL2 | Louise Daugherty Source Expert review Amber was added to NBEAL2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | MYH9 | Louise Daugherty Source Expert review Amber was added to MYH9. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | MTHFD1 | Louise Daugherty Source Expert review Red was added to MTHFD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | MSN | Louise Daugherty Source Expert review Red was added to MSN. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | MPL | Louise Daugherty Source Expert review Green was added to MPL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | MPIG6B | Louise Daugherty Source Expert review Red was added to MPIG6B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | MECOM | Louise Daugherty Source Expert review Green was added to MECOM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | LYST | Louise Daugherty Source Expert review Red was added to LYST. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | LAMTOR2 | Louise Daugherty Source Expert review Red was added to LAMTOR2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | KDSR | Louise Daugherty Source Expert review Red was added to KDSR. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | ITGB3 | Louise Daugherty Source Expert review Red was added to ITGB3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | ITGA2B | Louise Daugherty Source Expert review Red was added to ITGA2B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | HTRA2 | Louise Daugherty Source Expert review Red was added to HTRA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | HOXA11 | Louise Daugherty Source Expert review Red was added to HOXA11. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | GP9 | Louise Daugherty Source Expert review Amber was added to GP9. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | GP1BB | Louise Daugherty Source Expert review Amber was added to GP1BB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | GP1BA | Louise Daugherty Source Expert review Amber was added to GP1BA. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | GNE | Louise Daugherty Source Expert review Red was added to GNE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | GINS1 | Louise Daugherty Source Expert review Red was added to GINS1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | GFI1 | Louise Daugherty Source Expert review Green was added to GFI1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | GATA1 | Louise Daugherty Source Expert review Green was added to GATA1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | FYB1 | Louise Daugherty Source Expert review Green was added to FYB1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | FLNA | Louise Daugherty Source Expert review Red was added to FLNA. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | FLI1 | Louise Daugherty Source Expert review Amber was added to FLI1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | ETV6 | Louise Daugherty Source Expert review Green was added to ETV6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | DIAPH1 | Louise Daugherty Source Expert review Red was added to DIAPH1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | CYCS | Louise Daugherty Source Expert review Green was added to CYCS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | CLPB | Louise Daugherty Source Expert review Red was added to CLPB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | CDC42 | Louise Daugherty Source Expert review Red was added to CDC42. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | CD40LG | Louise Daugherty Source Expert review Red was added to CD40LG. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | CD40 | Louise Daugherty Source Expert review Red was added to CD40. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | ARPC1B | Louise Daugherty Source Expert review Red was added to ARPC1B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | AP3B1 | Louise Daugherty Source Expert review Amber was added to AP3B1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | ANKRD26 | Louise Daugherty Source Expert review Green was added to ANKRD26. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | ADAMTS13 | Louise Daugherty Source Expert review Amber was added to ADAMTS13. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | ACTN1 | Louise Daugherty Source Expert review Amber was added to ACTN1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | ACTB | Louise Daugherty Source Expert review Red was added to ACTB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | ABCG8 | Louise Daugherty Source Expert review Amber was added to ABCG8. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.134 | ABCG5 | Louise Daugherty Source Expert review Amber was added to ABCG5. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.133 | VWF |
Louise Daugherty Mode of inheritance for gene VWF was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Added phenotypes von Willebrand disease, types 2A, 2B, 2M, and 2N, 613554; von Willibrand disease, type 3, 277480; von Willebrand disease, type 1, 193400 for gene: VWF |
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| Cytopenia - NOT Fanconi anaemia v0.133 | VPS13B |
Louise Daugherty Mode of inheritance for gene VPS13B was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Cohen syndrome, 216550 for gene: VPS13B |
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| Cytopenia - NOT Fanconi anaemia v0.133 | TCN2 |
Louise Daugherty Mode of inheritance for gene TCN2 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Transcobalamin II deficiency, 275350 for gene: TCN2 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | STK4 |
Louise Daugherty Mode of inheritance for gene STK4 was changed from to Unknown Added phenotypes T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations, 614868 for gene: STK4 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | SRC |
Louise Daugherty Mode of inheritance for gene SRC was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes ?Thrombocytopenia 6, 616937 for gene: SRC |
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| Cytopenia - NOT Fanconi anaemia v0.133 | SLFN14 |
Louise Daugherty Mode of inheritance for gene SLFN14 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Bleeding disorder, platelet-type, 20, 616913 for gene: SLFN14 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | RNU4ATAC |
Louise Daugherty Mode of inheritance for gene RNU4ATAC was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Roifman syndrome, 616651; Microcephalic osteodysplastic primordial dwarfism, type I, 210710 for gene: RNU4ATAC |
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| Cytopenia - NOT Fanconi anaemia v0.133 | PTPN11 |
Louise Daugherty Mode of inheritance for gene PTPN11 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Noonan syndrome 1, 163950 for gene: PTPN11 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | PSMB8 |
Louise Daugherty Mode of inheritance for gene PSMB8 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Proteasome-associated autoinflammatory syndrome 1 and digenic forms, 256040 for gene: PSMB8 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | MTHFD1 |
Louise Daugherty Mode of inheritance for gene MTHFD1 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia, 617780 for gene: MTHFD1 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | MSN |
Louise Daugherty Mode of inheritance for gene MSN was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females Added phenotypes Immunodeficiency 50, 300988 for gene: MSN |
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| Cytopenia - NOT Fanconi anaemia v0.133 | LYST |
Louise Daugherty Mode of inheritance for gene LYST was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Chediak-Higashi syndrome, 214500 for gene: LYST |
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| Cytopenia - NOT Fanconi anaemia v0.133 | LAMTOR2 |
Louise Daugherty Mode of inheritance for gene LAMTOR2 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Immunodeficiency due to defect in MAPBP-interacting protein, 610798 for gene: LAMTOR2 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | KDSR |
Louise Daugherty Mode of inheritance for gene KDSR was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Erythrokeratodermia variabilis et progressiva 4, 617526 for gene: KDSR |
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| Cytopenia - NOT Fanconi anaemia v0.133 | ITGB3 |
Louise Daugherty Mode of inheritance for gene ITGB3 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Glanzmann thrombasthenia, 273800 for gene: ITGB3 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | ITGA2B |
Louise Daugherty Mode of inheritance for gene ITGA2B was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Glanzmann thrombasthenia, 273800 for gene: ITGA2B |
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| Cytopenia - NOT Fanconi anaemia v0.133 | HTRA2 |
Louise Daugherty Mode of inheritance for gene HTRA2 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes 3-methylglutaconic aciduria, type VIII, 617248 for gene: HTRA2 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | GP9 |
Louise Daugherty Mode of inheritance for gene GP9 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Bernard-Soulier syndrome (includes macrothrombocytopenia); Bernard-Soulier syndrome, type C, 231200 for gene: GP9 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | GP1BB |
Louise Daugherty Mode of inheritance for gene GP1BB was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Bernard-Soulier syndrome, type B, 231200; Mild macrothrombocytopenia for gene: GP1BB |
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| Cytopenia - NOT Fanconi anaemia v0.133 | GNE |
Louise Daugherty Mode of inheritance for gene GNE was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Nonaka myopathy, 605820 for gene: GNE |
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| Cytopenia - NOT Fanconi anaemia v0.133 | GINS1 |
Louise Daugherty Mode of inheritance for gene GINS1 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Immunodeficiency 55, 617827 for gene: GINS1 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | FLNA | Louise Daugherty Mode of inheritance for gene FLNA was changed from to Unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.133 | FLI1 |
Louise Daugherty Mode of inheritance for gene FLI1 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Added phenotypes Bleeding disorder, platelet-type, 21, 617443 for gene: FLI1 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | DIAPH1 |
Louise Daugherty Mode of inheritance for gene DIAPH1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Macrothrombocytopenia and hearing loss; Deafness, autosomal dominant 1, 124900 for gene: DIAPH1 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | CLPB |
Louise Daugherty Mode of inheritance for gene CLPB was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, 616271 for gene: CLPB |
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| Cytopenia - NOT Fanconi anaemia v0.133 | CDC42 |
Louise Daugherty Mode of inheritance for gene CDC42 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Takenouchi-Kosaki syndrome, 616737 for gene: CDC42 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | CD40LG |
Louise Daugherty Mode of inheritance for gene CD40LG was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females Added phenotypes Immunodeficiency, X-linked, with hyper-IgM, 308230 for gene: CD40LG |
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| Cytopenia - NOT Fanconi anaemia v0.133 | CD40 |
Louise Daugherty Mode of inheritance for gene CD40 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Immunodeficiency with hyper-IgM, type 3, 606843 for gene: CD40 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | ARPC1B |
Louise Daugherty Mode of inheritance for gene ARPC1B was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, 617718 for gene: ARPC1B |
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| Cytopenia - NOT Fanconi anaemia v0.133 | AP3B1 |
Louise Daugherty Mode of inheritance for gene AP3B1 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Hermansky-Pudlak syndrome 2, 608233 for gene: AP3B1 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | ADAMTS13 |
Louise Daugherty Mode of inheritance for gene ADAMTS13 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Thrombotic thrombocytopenic purpura, familial, 274150 for gene: ADAMTS13 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | ACTN1 |
Louise Daugherty Mode of inheritance for gene ACTN1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Bleeding disorder, platelet-type, 15, 615193; Macrothrombocytopenia for gene: ACTN1 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | ACTB |
Louise Daugherty Mode of inheritance for gene ACTB was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Baraitser-Winter syndrome 1 with macrothrombocytopenia; Baraitser-Winter syndrome 1, 243310 for gene: ACTB |
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| Cytopenia - NOT Fanconi anaemia v0.133 | ABCG8 |
Louise Daugherty Mode of inheritance for gene ABCG8 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Sitosterolemia with macrothrombocytopenia; Sitosterolemia, 210250 for gene: ABCG8 |
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| Cytopenia - NOT Fanconi anaemia v0.133 | ABCG5 |
Louise Daugherty Mode of inheritance for gene ABCG5 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Sitosterolemia with macrothrombocytopenia; Sitosterolemia, 210250 for gene: ABCG5 |
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| Cytopenia - NOT Fanconi anaemia v0.132 | VWF |
Louise Daugherty gene: VWF was added gene: VWF was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: VWF was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | VPS13B |
Louise Daugherty gene: VPS13B was added gene: VPS13B was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: VPS13B was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | TUBB1 |
Louise Daugherty Source Wessex and West Midlands GLH was added to TUBB1. Source Yorkshire and North East GLH was added to TUBB1. Source North West GLH was added to TUBB1. |
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| Cytopenia - NOT Fanconi anaemia v0.132 | THPO | Louise Daugherty Source Wessex and West Midlands GLH was added to THPO. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.132 | TCN2 |
Louise Daugherty gene: TCN2 was added gene: TCN2 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: TCN2 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | STK4 |
Louise Daugherty gene: STK4 was added gene: STK4 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: STK4 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | STIM1 |
Louise Daugherty Source Wessex and West Midlands GLH was added to STIM1. Source Yorkshire and North East GLH was added to STIM1. Source North West GLH was added to STIM1. |
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| Cytopenia - NOT Fanconi anaemia v0.132 | SRC |
Louise Daugherty gene: SRC was added gene: SRC was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: SRC was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | SMARCAL1 |
Louise Daugherty Source Wessex and West Midlands GLH was added to SMARCAL1. Source Yorkshire and North East GLH was added to SMARCAL1. Source North West GLH was added to SMARCAL1. |
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| Cytopenia - NOT Fanconi anaemia v0.132 | SLFN14 |
Louise Daugherty gene: SLFN14 was added gene: SLFN14 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: SLFN14 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | SLC37A4 |
Louise Daugherty Source Wessex and West Midlands GLH was added to SLC37A4. Source Yorkshire and North East GLH was added to SLC37A4. Source North West GLH was added to SLC37A4. |
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| Cytopenia - NOT Fanconi anaemia v0.132 | RUNX1 |
Louise Daugherty Source Wessex and West Midlands GLH was added to RUNX1. Source Yorkshire and North East GLH was added to RUNX1. Source North West GLH was added to RUNX1. |
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| Cytopenia - NOT Fanconi anaemia v0.132 | RNU4ATAC |
Louise Daugherty gene: RNU4ATAC was added gene: RNU4ATAC was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: RNU4ATAC was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | RBM8A | Louise Daugherty Source Wessex and West Midlands GLH was added to RBM8A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.132 | PTPN11 |
Louise Daugherty gene: PTPN11 was added gene: PTPN11 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: PTPN11 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | PSMB8 |
Louise Daugherty gene: PSMB8 was added gene: PSMB8 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: PSMB8 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | NBEAL2 |
Louise Daugherty Source Wessex and West Midlands GLH was added to NBEAL2. Source Yorkshire and North East GLH was added to NBEAL2. Source North West GLH was added to NBEAL2. |
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| Cytopenia - NOT Fanconi anaemia v0.132 | MYH9 |
Louise Daugherty Source Wessex and West Midlands GLH was added to MYH9. Source Yorkshire and North East GLH was added to MYH9. Source North West GLH was added to MYH9. |
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| Cytopenia - NOT Fanconi anaemia v0.132 | MTHFD1 |
Louise Daugherty gene: MTHFD1 was added gene: MTHFD1 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: MTHFD1 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | MSN |
Louise Daugherty gene: MSN was added gene: MSN was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: MSN was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | MPL | Louise Daugherty Source Wessex and West Midlands GLH was added to MPL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.132 | MPIG6B | Louise Daugherty Source Yorkshire and North East GLH was added to MPIG6B. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.132 | MECOM | Louise Daugherty Source Wessex and West Midlands GLH was added to MECOM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.132 | LYST |
Louise Daugherty gene: LYST was added gene: LYST was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: LYST was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | LAMTOR2 |
Louise Daugherty gene: LAMTOR2 was added gene: LAMTOR2 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: LAMTOR2 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | KDSR |
Louise Daugherty gene: KDSR was added gene: KDSR was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: KDSR was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | ITGB3 |
Louise Daugherty gene: ITGB3 was added gene: ITGB3 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: ITGB3 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | ITGA2B |
Louise Daugherty gene: ITGA2B was added gene: ITGA2B was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: ITGA2B was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | HTRA2 |
Louise Daugherty gene: HTRA2 was added gene: HTRA2 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: HTRA2 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | HOXA11 |
Louise Daugherty Source Wessex and West Midlands GLH was added to HOXA11. Source North West GLH was added to HOXA11. |
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| Cytopenia - NOT Fanconi anaemia v0.132 | GP9 |
Louise Daugherty gene: GP9 was added gene: GP9 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: GP9 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | GP1BB |
Louise Daugherty gene: GP1BB was added gene: GP1BB was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: GP1BB was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | GP1BA |
Louise Daugherty Source Wessex and West Midlands GLH was added to GP1BA. Source Yorkshire and North East GLH was added to GP1BA. Source North West GLH was added to GP1BA. |
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| Cytopenia - NOT Fanconi anaemia v0.132 | GNE |
Louise Daugherty gene: GNE was added gene: GNE was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: GNE was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | GINS1 |
Louise Daugherty gene: GINS1 was added gene: GINS1 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: GINS1 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | FYB1 | Louise Daugherty Source Wessex and West Midlands GLH was added to FYB1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.132 | FLNA |
Louise Daugherty gene: FLNA was added gene: FLNA was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: FLNA was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | FLI1 |
Louise Daugherty gene: FLI1 was added gene: FLI1 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: FLI1 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | ETV6 |
Louise Daugherty Source Wessex and West Midlands GLH was added to ETV6. Source North West GLH was added to ETV6. |
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| Cytopenia - NOT Fanconi anaemia v0.132 | DIAPH1 |
Louise Daugherty gene: DIAPH1 was added gene: DIAPH1 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: DIAPH1 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | CYCS |
Louise Daugherty Source Wessex and West Midlands GLH was added to CYCS. Source North West GLH was added to CYCS. |
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| Cytopenia - NOT Fanconi anaemia v0.132 | CLPB |
Louise Daugherty gene: CLPB was added gene: CLPB was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: CLPB was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | CDC42 |
Louise Daugherty gene: CDC42 was added gene: CDC42 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: CDC42 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | CD40LG |
Louise Daugherty gene: CD40LG was added gene: CD40LG was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: CD40LG was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | CD40 |
Louise Daugherty gene: CD40 was added gene: CD40 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: CD40 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | ARPC1B |
Louise Daugherty gene: ARPC1B was added gene: ARPC1B was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: ARPC1B was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | AP3B1 |
Louise Daugherty gene: AP3B1 was added gene: AP3B1 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: AP3B1 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | ANKRD26 |
Louise Daugherty Source Wessex and West Midlands GLH was added to ANKRD26. Source North West GLH was added to ANKRD26. |
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| Cytopenia - NOT Fanconi anaemia v0.132 | ADAMTS13 |
Louise Daugherty gene: ADAMTS13 was added gene: ADAMTS13 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: ADAMTS13 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | ACTN1 |
Louise Daugherty gene: ACTN1 was added gene: ACTN1 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: ACTN1 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | ACTB |
Louise Daugherty gene: ACTB was added gene: ACTB was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: ACTB was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | ABCG8 |
Louise Daugherty gene: ABCG8 was added gene: ABCG8 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: ABCG8 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.132 | ABCG5 |
Louise Daugherty gene: ABCG5 was added gene: ABCG5 was added to Cytopenia - NOT Fanconi anaemia. Sources: Wessex and West Midlands GLH,Yorkshire and North East GLH,London South GLH,North West GLH,NHS GMS Mode of inheritance for gene: ABCG5 was set to |
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| Cytopenia - NOT Fanconi anaemia v0.131 | TUBB1 | Louise Daugherty Phenotypes for gene: TUBB1 were changed from 613112 Macrothrombocytopenia to Macrothrombocytopenia, 613112 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.130 | STIM1 | Louise Daugherty Phenotypes for gene: STIM1 were changed from 185070 Stormorken syndrome to Stormorken syndrome, 185070 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.129 | SMARCAL1 | Louise Daugherty Phenotypes for gene: SMARCAL1 were changed from 242900 Schimke immunoosseous dysplasia to Schimke immunoosseous dysplasia, 242900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.128 | SLC37A4 | Louise Daugherty Phenotypes for gene: SLC37A4 were changed from 232220 Glycogen storage disease Ib to Glycogen storage disease Ib, 232220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.127 | RUNX1 | Louise Daugherty Phenotypes for gene: RUNX1 were changed from 601399 Platelet disorder, familial, with associated myeloid malignancy to Platelet disorder, familial, with associated myeloid malignancy, 601399 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.126 | NBEAL2 | Louise Daugherty Phenotypes for gene: NBEAL2 were changed from 139090 Gray platelet syndrome to Gray platelet syndrome, 139090 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.125 | MYH9 | Louise Daugherty Phenotypes for gene: MYH9 were changed from 155100 Macrothrombocytopenia to Macrothrombocytopenia, 155100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.124 | HOXA11 | Louise Daugherty Phenotypes for gene: HOXA11 were changed from 605432 Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 to Radioulnar synostosis with amegakaryocytic thrombocytopenia 1, 605432 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.123 | GP1BA | Louise Daugherty Phenotypes for gene: GP1BA were changed from 231200 Bernard-Soulier syndrome, type A1 to Bernard-Soulier syndrome, type A1, 231200; Mild macrothrombocytopenia; Platelet type VWD, mild thrombocytopenia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.122 | CYCS | Louise Daugherty Phenotypes for gene: CYCS were changed from 612004 Thrombocytopenia 4; Thrombocytopenia to Thrombocytopenia 4, 612004; Thrombocytopenia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cytopenia - NOT Fanconi anaemia v0.121 | ANKRD26 | Louise Daugherty Phenotypes for gene: ANKRD26 were changed from 188000 Thrombocytopenia 2 to Thrombocytopenia 2, 188000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Polycystic liver disease v0.8 | STN1 | Ivone Leong changed review comment from: Comment when marking as ready: After discussion with Anna de Burca (Genomics England) and Bill Griffiths (Cambridge University Hospitals), it was decided that RTEL1 will remain as an amber gene.; to: Comment when marking as ready: After discussion with Anna de Burca (Genomics England) and Bill Griffiths (Cambridge University Hospitals), it was decided that STN1 will remain as an amber gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Polycystic liver disease v0.8 | TERC | Ivone Leong changed review comment from: Comment when marking as ready: After discussion with Anna de Burca (Genomics England) and Bill Griffiths (Cambridge University Hospitals), it was decided that RTEL1 will remain as an amber gene.; to: Comment when marking as ready: After discussion with Anna de Burca (Genomics England) and Bill Griffiths (Cambridge University Hospitals), it was decided that TERC will remain as an amber gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Polycystic liver disease v0.8 | TERT | Ivone Leong changed review comment from: Comment when marking as ready: After discussion with Anna de Burca (Genomics England) and Bill Griffiths (Cambridge University Hospitals), it was decided that RTEL1 will remain as an amber gene.; to: Comment when marking as ready: After discussion with Anna de Burca (Genomics England) and Bill Griffiths (Cambridge University Hospitals), it was decided that TERT will remain as an amber gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.390 | SETX | Catherine Snow reviewed gene: SETX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyotrophic lateral sclerosis 4, juvenile, 602433, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, 606002; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.410 | SKIV2L | Catherine Snow Classified gene: SKIV2L as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.410 | SKIV2L | Catherine Snow Gene: skiv2l has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.409 | SKIV2L | Catherine Snow reviewed gene: SKIV2L: Rating: GREEN; Mode of pathogenicity: None; Publications: 22444670, 30397475; Phenotypes: Trichohepatoenteric syndrome 2, 614602; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.390 | SKIV2L | Catherine Snow Classified gene: SKIV2L as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.390 | SKIV2L | Catherine Snow Gene: skiv2l has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.389 | SKIV2L | Catherine Snow reviewed gene: SKIV2L: Rating: GREEN; Mode of pathogenicity: None; Publications: 22444670, 30397475; Phenotypes: Trichohepatoenteric syndrome 2, 614602; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.409 | SLC12A3 | Catherine Snow Classified gene: SLC12A3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.409 | SLC12A3 | Catherine Snow Gene: slc12a3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.408 | SLC12A3 | Catherine Snow reviewed gene: SLC12A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22009145; Phenotypes: Gitelman syndrome, 263800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.389 | SLC12A3 | Catherine Snow Classified gene: SLC12A3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.389 | SLC12A3 | Catherine Snow Gene: slc12a3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.388 | SLC12A3 | Catherine Snow Classified gene: SLC12A3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.388 | SLC12A3 | Catherine Snow Gene: slc12a3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.387 | SLC12A3 | Catherine Snow reviewed gene: SLC12A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22009145; Phenotypes: Gitelman syndrome, 263800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.408 | SLC18A2 | Catherine Snow Classified gene: SLC18A2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.408 | SLC18A2 | Catherine Snow Gene: slc18a2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.407 | SLC18A2 | Catherine Snow reviewed gene: SLC18A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31240161, 23363473, 26497564, 28716265; Phenotypes: ?Parkinsonism-dystonia, infantile, 2, 618049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.387 | SLC18A2 | Catherine Snow Classified gene: SLC18A2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.387 | SLC18A2 | Catherine Snow Gene: slc18a2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.387 | SLC18A2 | Catherine Snow Classified gene: SLC18A2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.387 | SLC18A2 | Catherine Snow Gene: slc18a2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.386 | SLC18A2 | Catherine Snow reviewed gene: SLC18A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31240161, 23363473, 26497564, 28716265; Phenotypes: ?Parkinsonism-dystonia, infantile, 2, 618049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.407 | SLC35A2 | Catherine Snow Classified gene: SLC35A2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.407 | SLC35A2 | Catherine Snow Gene: slc35a2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.386 | SLC35A2 | Catherine Snow Classified gene: SLC35A2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.386 | SLC35A2 | Catherine Snow Gene: slc35a2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.386 | SLC35A2 | Catherine Snow Classified gene: SLC35A2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.386 | SLC35A2 | Catherine Snow Gene: slc35a2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.406 | SLC35A2 | Catherine Snow reviewed gene: SLC35A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30746764; Phenotypes: Congenital disorder of glycosylation, type IIm, 300896; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.385 | SLC35A2 | Catherine Snow reviewed gene: SLC35A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30746764; Phenotypes: Congenital disorder of glycosylation, type IIm, 300896; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.406 | SLC3A1 | Catherine Snow Classified gene: SLC3A1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.406 | SLC3A1 | Catherine Snow Gene: slc3a1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.405 | SLC3A1 | Catherine Snow reviewed gene: SLC3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12239244; Phenotypes: Cystinuria, 220100; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.385 | SLC3A1 | Catherine Snow Classified gene: SLC3A1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.385 | SLC3A1 | Catherine Snow Gene: slc3a1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.384 | SLC3A1 | Catherine Snow reviewed gene: SLC3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12239244; Phenotypes: Cystinuria, 220100; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.384 | SLC6A3 |
Catherine Snow changed review comment from: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Promoted from Amber to Green. SLC7A9 is associated with an appropriate phenotype on OMIM. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status.; to: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Promoted from Amber to Green. SLC6A3 is associated with an appropriate phenotype on OMIM. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status. |
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| Undiagnosed metabolic disorders v1.405 | SLC6A3 | Catherine Snow Phenotypes for gene: SLC6A3 were changed from Dopamine transporter deficiency syndrome (Other disorders of neurotransmitter metabolism) ; Early onset dystonia; Intellectual disability; Parkinson Disease and Complex Parkinsonism to Parkinsonism-dystonia, infantile, 1, 613135; Dopamine transporter deficiency syndrome (Other disorders of neurotransmitter metabolism); Early onset dystonia; Intellectual disability; Parkinson Disease and Complex Parkinsonism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.404 | SLC6A3 | Catherine Snow Publications for gene: SLC6A3 were set to 27604308 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.403 | SLC6A3 | Catherine Snow Classified gene: SLC6A3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.403 | SLC6A3 | Catherine Snow Added comment: Comment on list classification: ted from Amber to Green. SLC6A3 is associated with an appropriate phenotype on OMIM. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.403 | SLC6A3 | Catherine Snow Gene: slc6a3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.384 | SLC6A3 | Catherine Snow Classified gene: SLC6A3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.384 | SLC6A3 | Catherine Snow Gene: slc6a3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.383 | SLC6A3 | Catherine Snow edited their review of gene: SLC6A3: Changed publications: 21112253; Changed phenotypes: Parkinsonism-dystonia, infantile, 1, 613135 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.383 | SLC6A3 | Catherine Snow reviewed gene: SLC6A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.383 | RNASET2 | Ivone Leong reviewed gene: RNASET2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.383 | SDHC |
Ivone Leong changed review comment from: his gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. This gene is present as an Amber gene on the Mitochondrial disorder with complex II deficiency (v 1.0) and Possible mitochondrial disorder - nuclear genes (v 1.12). Both GMS panels have been signed off by the GMS Metabolic Consensus Specialist Test Group. Therefore, this gene will remain Amber until further evidence is available.; to: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. This gene is present as an Amber gene on the Mitochondrial disorder with complex II deficiency (v 1.0) and Possible mitochondrial disorder - nuclear genes (v 1.12). Both GMS panels have been signed off by the GMS Metabolic Consensus Specialist Test Group. Therefore, this gene will remain Amber until further evidence is available. |
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| Undiagnosed metabolic disorders v1.402 | RBP4 | Ivone Leong Classified gene: RBP4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.402 | RBP4 | Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green. RBP4 is associated with retinoid metabolism on OMIM, but not on Gene2Phenotype. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.402 | RBP4 | Ivone Leong Gene: rbp4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.383 | RBP4 | Ivone Leong Classified gene: RBP4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.383 | RBP4 | Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green. RBP4 is associated with retinoid metabolism on OMIM, but not on Gene2Phenotype. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.383 | RBP4 | Ivone Leong Gene: rbp4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.38 | PHEX | Eleanor Williams Added comment: Comment on mode of inheritance: Following XLD mode of inhertiance in OMIM, so changing to X-Linked: hemizyous mutation in males, monoallelic in females. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.38 | PHEX | Eleanor Williams Mode of inheritance for gene: PHEX was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.37 | SLC7A9 | Eleanor Williams Phenotypes for gene: SLC7A9 were changed from Cystinuria to Cystinuria 220100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.36 | SLC3A1 | Eleanor Williams Phenotypes for gene: SLC3A1 were changed from Cystinuria to Cystinuria 220100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.35 | SLC22A12 | Eleanor Williams changed review comment from: Comment on mode of inheritance: The evidence for biallelic inheritance is stronger so setting to this for now.; to: Comment on mode of inheritance: The evidence for biallelic inheritance is stronger so setting to this for now. AR in OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.35 | CLCN5 | Eleanor Williams changed review comment from: Comment on Mode of Inheritance - PMID: 25907713 reports that female carriers can have mild symptoms of Dent disease so Xlinked (monoalllelic in females) may be more appropriate. However, in OMIM the mode of inheritance for Hypophosphatemic rickets, Nephrolithiasis, type I and Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis) is XLR so keeping as Xlinked (biallelic in females) just now.; to: Comment on Mode of Inheritance - PMID: 25907713 reports that female carriers can have mild symptoms of Dent disease so Xlinked (monoalllelic in females) may be more appropriate. However, in OMIM the mode of inheritance for Dents disease, Hypophosphatemic rickets, Nephrolithiasis, type I and Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis is XLR so keeping as Xlinked (biallelic in females) just now. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.35 | SLC2A9 | Eleanor Williams Phenotypes for gene: SLC2A9 were changed from to Hypouricemia, renal, 2, 612076 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.34 | SLC2A9 | Eleanor Williams Publications for gene: SLC2A9 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.33 | SLC2A9 | Eleanor Williams Classified gene: SLC2A9 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.33 | SLC2A9 | Eleanor Williams Added comment: Comment on list classification: Changing rating from red to green. 3 unrelated cases with Hypouricemia, renal, with Nephrolithiasis in some family members. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.33 | SLC2A9 | Eleanor Williams Gene: slc2a9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.32 | SLC2A9 | Eleanor Williams Added comment: Comment on mode of inheritance: Both monoallelic and biallelic for Hypouricemia, renal. However, the reported cases with nephrolithiasis are homozygous. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.32 | SLC2A9 | Eleanor Williams Mode of inheritance for gene: SLC2A9 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.31 | SLC2A9 |
Eleanor Williams changed review comment from: Associated with Hypouricemia, renal, 2 #612076 (AD, AR) in OMIM. PMID: 19926891 - Dinour et al 2010 - studied two unrelated consanguineous families who had severe hereditary hypouricemia and did not have a URAT1 defect. Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. Nephrolithiasis was seen in some members of both families. PMID: 21256783 - Stiburkova et al 2011 - proband and her brother from a Czech family with renal hypouricemia have a one nucleotide homozygote insertion in exon 3 in the SLC2A9 gene resulting in a truncated protein (p.Ile118HisfsX27). The brother showed urolithiasis. PMID: 19026395 - Matsuo et al 2008 - report two loss-of-function heterozygous mutations in GLUT9 (SLC2A9)(R380W and R198C) in renal hypouricemic patients who have no URAT1 mutations but it is not reported whether they have Nephrocalcinosis/nephrolithiasis. PMID: 21810765 - 2 cases renal hypouricemia and variants in SLC2A9 - no nephrolithiasis reported PMID: 29486147 - 2 cases with renal hypouricemia and variants in SLC2A9 - no nephrolithiasis reported PMID: 27116386 - 1 case with renal hypouricemia and variant in SLC2A9 - no nephrolithiasis reported PMID: 24940677 - 1 case with renal hypouricaemia and variant in SLC2A9 - no mention of nepthrolithiasis Summary, clear association of variants in SLC2A9 with renal hypouricaemia . 3 cases reported with nepthrolithiasis/urothilthiasis but many more cases where it is not mentioned. ; to: Associated with Hypouricemia, renal, 2 #612076 (AD, AR) in OMIM. Cases with nepthrolithiasis: PMID: 19926891 - Dinour et al 2010 - studied two unrelated consanguineous families who had severe hereditary hypouricemia and did not have a URAT1 defect. Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. Nephrolithiasis was seen in some members of both families. PMID: 21256783 - Stiburkova et al 2011 - proband and her brother from a Czech family with renal hypouricemia have a one nucleotide homozygous insertion in exon 3 in the SLC2A9 gene resulting in a truncated protein (p.Ile118HisfsX27). The brother showed urolithiasis. Cases with no report of nepthrolithiasis: PMID: 19026395 - Matsuo et al 2008 - report two loss-of-function heterozygous mutations in GLUT9 (SLC2A9)(R380W and R198C) in renal hypouricemic patients who have no URAT1 mutations but it is not reported whether they have Nephrocalcinosis/nephrolithiasis. PMID: 21810765 - 2 cases renal hypouricemia and variants in SLC2A9 - no nephrolithiasis reported PMID: 29486147 - 2 cases with renal hypouricemia and variants in SLC2A9 - no nephrolithiasis reported PMID: 27116386 - 1 case with renal hypouricemia and variant in SLC2A9 - no nephrolithiasis reported PMID: 24940677 - 1 case with renal hypouricaemia and variant in SLC2A9 - no mention of nepthrolithiasis Summary, clear association of variants in SLC2A9 with renal hypouricaemia . 3 cases reported with nepthrolithiasis/urothilthiasis but many more cases where it is not mentioned. |
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| Nephrocalcinosis or nephrolithiasis v1.31 | SLC2A9 |
Eleanor Williams changed review comment from: Associated with Hypouricemia, renal, 2 #612076 (AD, AR) in OMIM. PMID: 19926891 - Dinour et al 2010 - studied two unrelated consanguineous families who had severe hereditary hypouricemia and did not have a URAT1 defect. Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. Nephrolithiasis was seen in some members of both families. PMID: 21256783 - Stiburkova et al 2011 - proband and her brother from a Czech family with renal hypouricemia have a one nucleotide homozygote insertion in exon 3 in the SLC2A9 gene resulting in a truncated protein (p.Ile118HisfsX27). The brother showed urolithiasis. PMID: 19026395 - Matsuo et al 2008 - report two loss-of-function heterozygous mutations in GLUT9 (SLC2A9)(R380W and R198C) in renal hypouricemic patients who have no URAT1 mutations but it is not reported whether they have Nephrocalcinosis/nephrolithiasis. PMID: 21810765 - 2 cases renal hypouricemia and variants in SLC2A9 - no nephrolithiasis reported PMID: 29486147 - 2 cases with renal hypouricemia and variants in SLC2A9 - no nephrolithiasis reported PMID: 27116386 - 1 case with renal hypouricemia and variant in SLC2A9 - no nephrolithiasis reported PMID: 24940677 - 1 case with renal hypouricaemia and variant in SLC2A9 - no mention of nepthrolithiasis Summary, clear association of variants in SLC2A9 with renal hypouricaemia . 3 cases reported with nepthrolithiasis/urothilthiasis but many more cases where it is not mentioned. ; to: Associated with Hypouricemia, renal, 2 #612076 (AD, AR) in OMIM. PMID: 19926891 - Dinour et al 2010 - studied two unrelated consanguineous families who had severe hereditary hypouricemia and did not have a URAT1 defect. Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. Nephrolithiasis was seen in some members of both families. PMID: 21256783 - Stiburkova et al 2011 - proband and her brother from a Czech family with renal hypouricemia have a one nucleotide homozygote insertion in exon 3 in the SLC2A9 gene resulting in a truncated protein (p.Ile118HisfsX27). The brother showed urolithiasis. PMID: 19026395 - Matsuo et al 2008 - report two loss-of-function heterozygous mutations in GLUT9 (SLC2A9)(R380W and R198C) in renal hypouricemic patients who have no URAT1 mutations but it is not reported whether they have Nephrocalcinosis/nephrolithiasis. PMID: 21810765 - 2 cases renal hypouricemia and variants in SLC2A9 - no nephrolithiasis reported PMID: 29486147 - 2 cases with renal hypouricemia and variants in SLC2A9 - no nephrolithiasis reported PMID: 27116386 - 1 case with renal hypouricemia and variant in SLC2A9 - no nephrolithiasis reported PMID: 24940677 - 1 case with renal hypouricaemia and variant in SLC2A9 - no mention of nepthrolithiasis Summary, clear association of variants in SLC2A9 with renal hypouricaemia . 3 cases reported with nepthrolithiasis/urothilthiasis but many more cases where it is not mentioned. |
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| Nephrocalcinosis or nephrolithiasis v1.31 | SLC22A12 | Eleanor Williams Classified gene: SLC22A12 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.31 | SLC22A12 | Eleanor Williams Added comment: Comment on list classification: Promoting from red to green. Sufficient number of cases with biallelic or compound heterozygous variants in this gene and a relevant phenotype reported. A few heterozygous cases also reported but the evidence is not so strong (asymptomatic family members with the same variant, only the SLC22A12 gene looked at). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.31 | SLC22A12 | Eleanor Williams Gene: slc22a12 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.30 | SLC22A12 | Eleanor Williams Phenotypes for gene: SLC22A12 were changed from to Hypouricemia, renal, 220150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.29 | SLC22A12 |
Eleanor Williams changed review comment from: Associated with Hypouricemia, renal #220150 (AR) in OMIM with Uric acid nephrolithiasis listed as a clinical feature. PMID: 29486147 - Claverie-Martin et al 2018 - report patients from 6 unrelated Spanish families with Renal hypouricemia and variants in SLC22A12. Nephrolithiasis was reported in one Roma patient with compound heterozygous variants in this gene. PMID: 29958533 - Vidanapathirana et al 2018 - report a 9 year old Sri Lankan boy with renal hypouricemia who presented with nephrolithiasis and haematuria. He was found to have a potentially deleterious missense variant c.1400C > T (p.T467 M, rs200104135) in heterozygous state. This variant has been previously identified in homozygous and/or compound heterozygous state with other causative SLC22A12 variant c.1245_1253del (p.L415_G417del) in Roma population. The genotype c.[1400C > T] was found in the proband, his sister and father (both asymptomatic). PMID: 18492088 - Ichida et al 2008 - identified SLC22A12 mutations in 66 of 71 Japanese patients with hypouricemia. A total of 13 mutations, including 3 novel mutations, were identified. Urolithiasis occurred in 5 of the patients with variants in SLC22A12. 4 were homozygous or compound heterozygous, one was heterozygous. One variant G774A/W258X was the most common variant and is thought to be a founder mutation. PMID: 15912381 - Cheong et al 2005 - studied the SLC22A12 gene in five Korean patients with idiopathic renal hypouricemia, 1 patient with a R90H substitution had uric acid urolithiasis. The variant was heterozygous.; to: Associated with Hypouricemia, renal #220150 (AR) in OMIM with Uric acid nephrolithiasis listed as a clinical feature. PMID: 29486147 - Claverie-Martin et al 2018 - report patients from 6 unrelated Spanish families with Renal hypouricemia and variants in SLC22A12. Nephrolithiasis was reported in one Roma patient with compound heterozygous variants in this gene (L415_G417del, T467M). PMID: 29958533 - Vidanapathirana et al 2018 - report a 9 year old Sri Lankan boy with renal hypouricemia who presented with nephrolithiasis and haematuria. He was found to have a potentially deleterious missense variant c.1400C > T (p.T467 M, rs200104135) in heterozygous state. This variant has been previously identified in homozygous and/or compound heterozygous state with other causative SLC22A12 variant c.1245_1253del (p.L415_G417del) in Roma population. The genotype c.[1400C > T] was found in the proband, his sister and father (both asymptomatic). PMID: 18492088 - Ichida et al 2008 - identified SLC22A12 mutations in 66 of 71 Japanese patients with hypouricemia. A total of 13 mutations, including 3 novel mutations, were identified. Urolithiasis occurred in 5 of the patients with variants in SLC22A12. 4 were homozygous or compound heterozygous, one was heterozygous. One variant G774A/W258X was the most common variant and is thought to be a founder mutation. PMID: 15912381 - Cheong et al 2005 - studied the SLC22A12 gene in five Korean patients with idiopathic renal hypouricemia, 1 patient with a R90H substitution had uric acid urolithiasis. The variant was heterozygous. |
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| Nephrocalcinosis or nephrolithiasis v1.29 | SLC22A12 | Eleanor Williams Publications for gene: SLC22A12 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.28 | SLC22A12 | Eleanor Williams Added comment: Comment on mode of inheritance: The evidence for biallelic inheritance is stronger so setting to this for now. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.28 | SLC22A12 | Eleanor Williams Mode of inheritance for gene: SLC22A12 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.203 | KIZ | Ivone Leong Classified gene: KIZ as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.203 | KIZ | Ivone Leong Added comment: Comment on list classification: Promoted from red to green based on evidence provided by Mohammed Abdallah (Divsion of Human Genetics, university of Cape Town). The gene was previously classified as non-coding because of problems with Ensembl grch37 release; however, that has been fixed now and it is an actual gene. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.203 | KIZ | Ivone Leong Gene: kiz has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.27 | PHEX | Eleanor Williams commented on gene: PHEX: Personal communication from Detlef Bockenhauer. They see nephrocalcinosis in ~50% patients. It clearly is also related to treatment, but probably an intrinsic part of the disease. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.27 | HPRT1 | Eleanor Williams Classified gene: HPRT1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.27 | HPRT1 | Eleanor Williams Added comment: Comment on list classification: Promoting from red to green. > 3 unrelated cases with variants in this gene and Lesch-Nyhan syndrome with nephrocalcinosis as a feature are reported. Numerous variants are reported. Two publications. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.27 | HPRT1 | Eleanor Williams Gene: hprt1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.26 | HPRT1 | Eleanor Williams Phenotypes for gene: HPRT1 were changed from to Lesch-Nyhan syndrome, 300322 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.25 | HPRT1 | Eleanor Williams Publications for gene: HPRT1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.24 | HNF4A | Eleanor Williams Classified gene: HNF4A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.24 | HNF4A | Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber. Only one paper (PMID: 24285859) reporting variants in this gene associated with Fanconi syndrome and nephrocalcinosis and all patients have the same variant. Another paper reports that individuals with that variant have congenital hyperinsulinism and Fanconi syndrome but no nephrocalcinosis, however they are younger than the previously reported patients. Rating amber for now until another report confirms the association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.24 | HNF4A | Eleanor Williams Gene: hnf4a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | FGF23 | Eleanor Williams commented on gene: FGF23: Leaving this gene red as no published evidence to date to associate variants in this gene with Nephrocalcinosis or nephrolithiasis. However, it is a likely contender so added the watchlist tag. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | FGF23 | Eleanor Williams Tag watchlist tag was added to gene: FGF23. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | STRADA | Eleanor Williams commented on gene: STRADA: Despite red rating from reviewer, there is some published evidence that nephrocalcinosis is reported in patients with Polyhydramnios, so keeping green rating for now. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | CLCN5 | Eleanor Williams commented on gene: CLCN5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Unexplained young onset end-stage renal disease v0.51 | CLCN5 | Eleanor Williams Mode of inheritance for gene: CLCN5 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | ZNF365 | Detlef Bockenhauer reviewed gene: ZNF365: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | VDR | Detlef Bockenhauer reviewed gene: VDR: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | TRPM6 | Detlef Bockenhauer reviewed gene: TRPM6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | STRADA | Detlef Bockenhauer reviewed gene: STRADA: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | SLC9A3 | Detlef Bockenhauer reviewed gene: SLC9A3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | SLC6A20 | Detlef Bockenhauer reviewed gene: SLC6A20: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | SLC6A19 | Detlef Bockenhauer reviewed gene: SLC6A19: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | SLC36A2 | Detlef Bockenhauer reviewed gene: SLC36A2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | GNA11 | Detlef Bockenhauer reviewed gene: GNA11: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | CLCNKA | Detlef Bockenhauer reviewed gene: CLCNKA: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | AP2S1 | Detlef Bockenhauer reviewed gene: AP2S1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | AGK | Detlef Bockenhauer reviewed gene: AGK: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | ADCY10 | Detlef Bockenhauer reviewed gene: ADCY10: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | HNF4A | Detlef Bockenhauer reviewed gene: HNF4A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | SLC2A9 | Detlef Bockenhauer reviewed gene: SLC2A9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | SLC22A12 | Detlef Bockenhauer reviewed gene: SLC22A12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | PHEX | Detlef Bockenhauer reviewed gene: PHEX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | HPRT1 | Detlef Bockenhauer reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | FGF23 | Detlef Bockenhauer reviewed gene: FGF23: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nephrocalcinosis or nephrolithiasis v1.23 | FAM20A | Detlef Bockenhauer reviewed gene: FAM20A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia and cerebellar anomalies - childhood onset v3.392 | Louise Daugherty Changed child panels to: Inborn errors of metabolism; Congenital disorders of glycosylation; Ataxia and cerebellar anomalies - narrow panel; Neurological ciliopathies | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.401 | SLC6A8 | Catherine Snow Classified gene: SLC6A8 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.401 | SLC6A8 | Catherine Snow Gene: slc6a8 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.400 | SLC6A8 | Catherine Snow reviewed gene: SLC6A8: Rating: GREEN; Mode of pathogenicity: None; Publications: 21660517; Phenotypes: Cerebral creatine deficiency syndrome 1, 300352; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.382 | SLC6A8 |
Catherine Snow changed review comment from: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Comment on list classification: Promoted from Amber to Green. SLC6A8 is associated with an appropriate phenotype on OMIM. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status.; to: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Promoted from Amber to Green. SLC6A8 is associated with an appropriate phenotype on OMIM. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status. |
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| Likely inborn error of metabolism v1.382 | SLC6A8 | Catherine Snow Classified gene: SLC6A8 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.382 | SLC6A8 | Catherine Snow Gene: slc6a8 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.381 | SLC6A8 | Catherine Snow reviewed gene: SLC6A8: Rating: GREEN; Mode of pathogenicity: None; Publications: 21660517; Phenotypes: Cerebral creatine deficiency syndrome 1, 300352; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.95 | RARA |
Ivone Leong gene: RARA was added gene: RARA was added to Structural eye disease. Sources: Expert list Mode of inheritance for gene: RARA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RARA were set to 31343737 Phenotypes for gene: RARA were set to Coloboma Review for gene: RARA was set to RED Added comment: Gene added on behalf of Nicola Ragge (Birmingham Women's and Children's NHS Foundation Hospital Trust). There is currently only 1 reported case of a de novo variant in RARA in a patient with symptoms overlapping those described in RARB patients (coloboma, muscular hypotonia, dilated pulmonary artery, ectopic kidney). Therefore, this gene has been given a Red rating until further evidence is available. Sources: Expert list |
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| Undiagnosed metabolic disorders v1.400 | SLC7A9 | Catherine Snow Classified gene: SLC7A9 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.400 | SLC7A9 | Catherine Snow Gene: slc7a9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Undiagnosed metabolic disorders v1.399 | SLC7A9 | Catherine Snow reviewed gene: SLC7A9: Rating: GREEN; Mode of pathogenicity: None; Publications: 12239244; Phenotypes: Cystinuria, 220100; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.381 | SLC7A9 | Catherine Snow Classified gene: SLC7A9 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.381 | SLC7A9 | Catherine Snow Gene: slc7a9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.380 | SLC7A9 | Catherine Snow Publications for gene: SLC7A9 were set to 27604308; 24816252 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v1.379 | SLC7A9 | Catherine Snow reviewed gene: SLC7A9: Rating: GREEN; Mode of pathogenicity: None; Publications: 12239244; Phenotypes: Cystinuria, 220100; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.136 | RASGRP1 | Louise Daugherty Phenotypes for gene: RASGRP1 were changed from Recurrent pneumonia, herpesvirus infections, EBV associated lymphoma; Diseases of Immune Dysregulation; EBV-induced lymphoma; Immunodeficiency; Immunodeficiency 64, 618534 to Recurrent pneumonia, herpesvirus infections, EBV associated lymphoma; Diseases of Immune Dysregulation; EBV-induced lymphoma; Immunodeficiency; Immunodeficiency 64, 618534; Immunodeficiency; immunde dysregulation; EBV-induced lymphoma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.135 | POMP | Louise Daugherty Phenotypes for gene: POMP were changed from CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome); Proteasome-associated autoinflammatory syndrome 2, 618048 to CANDLE syndrome (Autoinflammation, lipodystrophy, and dermatosis syndrome); Proteasome-associated autoinflammatory syndrome 2, 618048; combined immunodeficiency with autoinflammation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.134 | POMP | Louise Daugherty Publications for gene: POMP were set to 26524591 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v1.133 | POMP | Louise Daugherty Mode of inheritance for gene: POMP was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary spastic paraplegia v1.207 | PCYT2 | Louise Daugherty Classified gene: PCYT2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary spastic paraplegia v1.207 | PCYT2 | Louise Daugherty Added comment: Comment on list classification: New gene for HSP. There are more than 3 unrelated cases to support the HSP phenotype caused by homozygous mutation in the gene encoding phosphoethanolamine cytidylyltransferase | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary spastic paraplegia v1.207 | PCYT2 | Louise Daugherty Gene: pcyt2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary spastic paraplegia v1.206 | PCYT2 |
Louise Daugherty gene: PCYT2 was added gene: PCYT2 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCYT2 were set to 31637422 Phenotypes for gene: PCYT2 were set to Complex hereditary spastic paraplegia Review for gene: PCYT2 was set to GREEN Added comment: New publication (2019) : Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia: Vaz, Frédéric M et.al., PMID: 31637422. Identified five individuals with biallelic PCYT2 variants clinically characterized by global developmental delay with regression, spastic para- or tetraparesis, epilepsy and progressive cerebral and cerebellar atrophy. CTP:phosphoethanolamine cytidylyltransferase (ET) is encoded by the PCYT2 gene. Using patient fibroblasts they demonstrated that the variants were hypomorphic, resulting in altered but residual ET protein levels and concomitant reduced enzyme activity without affecting mRNA levels. The significantly better survival of hypomorphic CRISPR- Cas9 generated pcyt2 zebrafish knockout compared to a complete knockout, in conjunction with previously described data on the Pcyt2 mouse model, indicates that complete loss of ET function may be incompatible with life in vertebrates. Lipidomic analysis revealed profound lipid abnormalities in patient fibroblasts impacting both neutral etherlipid and etherphospholipid metabolism. Plasma lipidomics studies also identified changes in etherlipids that have the potential to be used as biomarkers for ET deficiency. The data establishes that PCYT2 as a disease gene for a new complex hereditary spastic paraplegia and confirmed that etherlipid homeostasis is important for the development and function of the brain. Sources: Literature |
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| Structural eye disease v0.94 | NAA10 | Ivone Leong Classified gene: NAA10 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.94 | NAA10 | Ivone Leong Added comment: Comment on list classification: Promoted to Green based on expert review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.94 | NAA10 | Ivone Leong Gene: naa10 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.202 | KIZ | Ivone Leong Phenotypes for gene: KIZ were changed from Retinitis pigmentosa 69 to Retinitis pigmentosa 69, 615780; HP:0000556; HP:0000510 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.201 | KIZ | Ivone Leong Mode of inheritance for gene: KIZ was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.200 | KIZ | Ivone Leong Publications for gene: KIZ were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.128 | GLB1 | Louise Daugherty Classified gene: GLB1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.128 | GLB1 | Louise Daugherty Added comment: Comment on list classification: Rated Amber until further review/agreement with the Neurology Test Group. To be reviewed before panel sign off | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.128 | GLB1 | Louise Daugherty Gene: glb1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.127 | GLB1 | Louise Daugherty Added comment: Comment on publications: added publications to support gene-phenotype | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.127 | GLB1 | Louise Daugherty Publications for gene: GLB1 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset dystonia, chorea or related movement disorder v0.126 | GLB1 |
Louise Daugherty gene: GLB1 was added gene: GLB1 was added to Adult onset movement disorder. Sources: Expert Review Mode of inheritance for gene: GLB1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GLB1 were set to GM1-gangliosidosis, type III, 230650 Review for gene: GLB1 was set to GREEN Added comment: New Green gene suggested by Dr Julia Rankin, Consultant in Clinical Genetics (Royal Devon and Exeter NHS Foundation Trust). Adults with GM1 gangliosidosis can present with dystonia and parkinsonism. Sources: Expert Review |
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| Early onset or syndromic epilepsy v1.398 | CLN6 | Rebecca Foulger commented on gene: CLN6: PMID:30561534. Berkovic et al., 2019 report phenotypes of patients with CLN6 pathogenic variants from 13 unrelated families (homozygous in 4 families and compound het in 9 families). The typical presentation was progressive myoclonus epilepsy with debilitating myoclonic seizures and relatively infrequent tonic-clonic seizures. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.398 | CLN6 | Rebecca Foulger Publications for gene: CLN6 were set to 21549341; 31029456; 31216804 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1093 | SIX3 | Rebecca Foulger Phenotypes for gene: SIX3 were changed from Holoprosencephaly-2, 157170Schizensephaly, 269160; HOLOPROSENCEPHALY to Holoprosencephaly-2, 157170; Schizensephaly, 269160; HOLOPROSENCEPHALY | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.397 | SETD5 | Rebecca Foulger Phenotypes for gene: SETD5 were changed from Mental retardation, autosomal dominant 23 to Mental retardation, autosomal dominant 23, 615761 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.396 | SETD5 | Rebecca Foulger Publications for gene: SETD5 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.395 | CLN6 | Rebecca Foulger Publications for gene: CLN6 were set to 21549341; 31029456 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.394 | CLN6 | Rebecca Foulger changed review comment from: PMID:31216804. Zhang et al. 2019 identify the pathogenic gene variants and clinical phenotype features of 26 children with progressive myoclonic epilepsy. 1 patient had a variant in CLN6 (full English text not avaialble).; to: PMID:31216804. Zhang et al. 2019 identify the pathogenic gene variants and clinical phenotype features of 26 children with progressive myoclonic epilepsy. 1 patient had a variant in CLN6 (full English text not available). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.394 | CLN6 | Rebecca Foulger commented on gene: CLN6: PMID:31216804. Zhang et al. 2019 identify the pathogenic gene variants and clinical phenotype features of 26 children with progressive myoclonic epilepsy. 1 patient had a variant in CLN6 (full English text not avaialble). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.394 | CLN6 | Rebecca Foulger commented on gene: CLN6: Additional case in PMID:31029456 (Matsumoto et al., 2019) of Japanese boy with a homozygous C.794_976del variant p. (Ser265del) in CLN6. Symptoms include focal seizures. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.394 | CLN6 | Rebecca Foulger Publications for gene: CLN6 were set to 21549341 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.393 | SGSH | Rebecca Foulger Classified gene: SGSH as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.393 | SGSH | Rebecca Foulger Added comment: Comment on list classification: Added SGSH to the panel with a Green rating: Green on the 'Inborn errors of metabolism' panel, and seizures are part of the MPS IIIA phenotype. Sufficient cases from the literature for inclusion on the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.393 | SGSH | Rebecca Foulger Gene: sgsh has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.392 | SGSH | Rebecca Foulger commented on gene: SGSH: PMID: 30593151 (Li et al., 2018) report an 8 year old female with developmental regression and seizures amongst her symptoms. She was diagnosed with autosomal recessive (AR) MPS IIIA with compound het variants in SGSH (c.1298G>A p.Arg433Gln and c.630 G>T p.Trp210Cys), inherited from each parent. The pathogenicity of c.630G>T has not been reported yet. c.1298G>A has been associated with MPS-IIIA previously. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.392 | SGSH | Rebecca Foulger commented on gene: SGSH: PMID:21061399: Valstar et al. 2010 retrospectively reviewed the clinical features of 92 patients with MPS IIIA, including 32 living and 60 deceased individuals. There was wide phenotypic variability but Epilepsy was reported in 53/80 patients with a median seizure age of 11 years (range, 1-43 years). Patients with a severe MPS IIIA phenotype developed epilepsy at a significantly earlier age compared to patients suffering from a more attenuated form of the disease. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v1.392 | SGSH |
Rebecca Foulger gene: SGSH was added gene: SGSH was added to Genetic epilepsy syndromes. Sources: Literature,Other Mode of inheritance for gene: SGSH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SGSH were set to 21061399; 30593151 Phenotypes for gene: SGSH were set to Mucopolysaccharidosis type IIIA (Sanfilippo A), 252900; seizures Review for gene: SGSH was set to GREEN Added comment: Added SGSH to the panel based on Green rating on the 'Inborn errors of metabolism' panel: seizures are a part of the Mucopolysaccharidosis phenotype. Sources: Literature, Other |
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| Intellectual disability v2.1092 | SVBP | Alistair Pagnamenta reviewed gene: SVBP: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31363758, 30607023; Phenotypes: brain abnormalities, microcephaly, intellectual disability, delayed gross motor development, spasticity, delayed speech development; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.17 | SLC2A1 | Louise Daugherty Publications for gene SLC2A1 were changed from to 19630075; 26598494; 10980529 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.17 | SLC1A3 | Louise Daugherty Publications for gene SLC1A3 were changed from to 19139306 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.17 | SCN4A | Louise Daugherty Publications for gene SCN4A were changed from to 18166706; 15534250; 19118277; 26700687 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal muscle channelopathy v0.17 | RYR1 | Louise Daugherty Publications for gene RYR1 were changed from to 12136074; 16163667; 20839240 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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