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Ataxia and cerebellar anomalies - narrow panel v2.161 UBTF Arina Puzriakova Publications for gene: UBTF were set to 29300972
Ataxia and cerebellar anomalies - narrow panel v2.160 UBTF Arina Puzriakova Mode of pathogenicity for gene: UBTF 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
Ataxia and cerebellar anomalies - narrow panel v2.159 UBTF Arina Puzriakova Classified gene: UBTF as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.159 UBTF Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 9 unrelated individuals from different ethnic backgrounds in literature with neuroregression including ataxia as an early feature due to a recurrent variant in this gene (PMIDs: 28777933; 29300972; 30517966; 31931739)
Ataxia and cerebellar anomalies - narrow panel v2.159 UBTF Arina Puzriakova Gene: ubtf has been classified as Amber List (Moderate Evidence).
Inherited white matter disorders v1.94 VPS11 Ivone Leong Classified gene: VPS11 as Green List (high evidence)
Inherited white matter disorders v1.94 VPS11 Ivone Leong Added comment: Comment on list classification: Promoted from Red to Green. This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. This gene is also rated Green on the Genetic epilepsy syndromes (Version 2.339).

It is also on the White matter disorders and cerebral calcification - narrow panel (Version 1.69) as an Amber gene with a recommendation to be promoted to Green. The following review is present:

"Recurrent homozygous variant, p.Cys846Gly identified in more than 10 families of Ashkenazi Jewish descent. One other variant reported in another family in PMID 27473128. Functional data.
Zornitza Stark (Australian Genomics), 16 Sep 2020"

There is enough evidence to support a gene-disease association.
Inherited white matter disorders v1.94 VPS11 Ivone Leong Gene: vps11 has been classified as Green List (High Evidence).
Inherited white matter disorders v1.93 VPS11 Ivone Leong Phenotypes for gene: VPS11 were changed from Leukodystrophy, hypomyelinating, 12, MIM#616683 to Leukodystrophy, hypomyelinating, 12, OMIM:616683
Inherited white matter disorders v1.92 VPS11 Ivone Leong Publications for gene: VPS11 were set to 26307567, 27120463
Ataxia and cerebellar anomalies - narrow panel v2.158 UBTF Arina Puzriakova Tag Q2_21_rating tag was added to gene: UBTF.
Ataxia and cerebellar anomalies - narrow panel v2.158 UBTF Arina Puzriakova reviewed gene: UBTF: 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: 28777933, 29300972, 30517966, 31931739; Phenotypes: Neurodegeneration, childhood-onset, with brain atrophy, OMIM:617672; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.1066 VPS11 Ivone Leong commented on gene: VPS11
Intellectual disability v3.1066 VPS11 Ivone Leong Tag watchlist was removed from gene: VPS11.
Tag Q2_21_rating tag was added to gene: VPS11.
White matter disorders and cerebral calcification - narrow panel v1.69 VPS11 Ivone Leong Tag Q2_21_rating tag was added to gene: VPS11.
White matter disorders and cerebral calcification - narrow panel v1.69 VPS11 Ivone Leong Classified gene: VPS11 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.69 VPS11 Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber. This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease assocation. This gene should be rated Green at the next review.
White matter disorders and cerebral calcification - narrow panel v1.69 VPS11 Ivone Leong Gene: vps11 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v1.68 VPS11 Ivone Leong Phenotypes for gene: VPS11 were changed from Leukodystrophy, hypomyelinating, 12, MIM#616683 to Leukodystrophy, hypomyelinating, 12, OMIM:616683
White matter disorders and cerebral calcification - narrow panel v1.67 VPS11 Ivone Leong Publications for gene: VPS11 were set to 26307567, 27120463
White matter disorders and cerebral calcification - narrow panel v1.66 UFM1 Ivone Leong Tag Q2_21_rating tag was added to gene: UFM1.
White matter disorders and cerebral calcification - narrow panel v1.66 UFM1 Ivone Leong Classified gene: UFM1 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.66 UFM1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be made Green at the next review.
White matter disorders and cerebral calcification - narrow panel v1.66 UFM1 Ivone Leong Gene: ufm1 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v1.65 UFM1 Ivone Leong Phenotypes for gene: UFM1 were changed from Leukodystrophy, hypomyelinating, 14, MIM# 617899 to Leukodystrophy, hypomyelinating, 14, OMIM:617899
White matter disorders and cerebral calcification - narrow panel v1.64 TUFM Ivone Leong commented on gene: TUFM: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
White matter disorders and cerebral calcification - narrow panel v1.64 TUFM Ivone Leong Tag Q2_21_rating tag was added to gene: TUFM.
White matter disorders and cerebral calcification - narrow panel v1.64 TUFM Ivone Leong Phenotypes for gene: TUFM were changed from Mitochondrial Leukoencephalopathy to Mitochondrial Leukoencephalopathy; Combined oxidative phosphorylation deficiency 4, OMIM:610678
Craniosynostosis v2.23 CHD7 Helen Lord gene: CHD7 was added
gene: CHD7 was added to Craniosynostosis. Sources: Expert Review
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD7 were set to 33844462; 30498854; 33288889
Phenotypes for gene: CHD7 were set to craniosynostosis
Review for gene: CHD7 was set to AMBER
Added comment: Newborn with bicoronal synostosis in whom a de novo CHD7 variant was identified c.6157C>T p.(Arg2053*) - NGS in proband, sanger sequencing used to exclude variant from the parents.
Other features included choanal atresia, markedly asymmetric malformed ears, folded and clipped off helix and triangular concha, retrognathia, marked facial asymetry with left eye constantly closed and hypoplastic toenails. Heart ultrasound revealed a small ASD and ophthalmoplegic exam revealed left retinal coloboma and asymmetrically placed eyes. CHARGE syndrome was suspected in this patient. Of note, this variant has been reported previoulsy in the literature in indivdiuals with CHARGE syndrome and no craniosynostosis was noted.
In this paper they mention two other cases reporteD in the literature in 2019/2020 where craniosynostosis was reported alongside a CHARGE phenotype and LOF variants were detected:
Siakallis et al, 2019: 30498854 c.3106C>T p.(Arg1036*) - CHARGE phenotype as well as synostosis of the coronal, left lambdoid and squamous sutures.
Tonne et al 2020: 33288889 c.7593dup p.(Thr2532fs) - CHARGE phenotype as well as late-onset sagittal synostosis.

Mouse studies indicate that CHD7 has a relevant dosage dependent role in the development of several craniofacial tissues - conditional knock out models showing among other bone and cartialage defects, frontal bone dysplasia.
Zebrafish model of CHARGE - flattening of the head is observed.
Sources: Expert Review
White matter disorders and cerebral calcification - narrow panel v1.63 TUFM Ivone Leong Added comment: Comment on publications: 25735936 - summarises the findings of exome analysis in 109 patients. 16 out of 42 patients with a high suspicion of a mitochondrial disorder were reported as having a disease causing mutation found in the mitochondrial gene panel - of which TUFM was one of the genes with the biochemical diagnosis of combined OXPHOS enzyme deficiency.;25655951;17160893 (case report)
White matter disorders and cerebral calcification - narrow panel v1.63 TUFM Ivone Leong Publications for gene: TUFM were set to 25735936 - summarises the findings of exome analysis in 109 patients. 16 out of 42 patients with a high suspicion of a mitochondrial disorder were reported as having a disease causing mutation found in the mitochondrial gene panel - of which TUFM was one of the genes with the biochemical diagnosis of combined OXPHOS enzyme deficiency.; 25655951; 17160893 (case report)
White matter disorders and cerebral calcification - narrow panel v1.62 TMEM63A Ivone Leong Tag Q2_21_rating tag was added to gene: TMEM63A.
White matter disorders and cerebral calcification - narrow panel v1.62 TMEM63A Ivone Leong Publications for gene: TMEM63A were set to 31587869
White matter disorders and cerebral calcification - narrow panel v1.61 TMEM63A Ivone Leong Classified gene: TMEM63A as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.61 TMEM63A Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype.

PMID: 33597727. 2 additional cases.

PMID: 33785861. 1 additional case.

There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
White matter disorders and cerebral calcification - narrow panel v1.61 TMEM63A Ivone Leong Gene: tmem63a has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v1.61 TMEM63A Ivone Leong Classified gene: TMEM63A as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.61 TMEM63A Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype.

PMID: 33597727. 2 additional cases.

PMID: 33785861. 1 additional case.

There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
White matter disorders and cerebral calcification - narrow panel v1.61 TMEM63A Ivone Leong Gene: tmem63a has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia or chorea or related movement disorder v1.98 FXN Sarah Leigh Phenotypes for gene: FXN were changed from Friedreich ataxia; Friedreich ataxia with retained reflexes, 229300 to Friedreich ataxia OMIM:229300; Friedreich ataxia with retained reflexes OMIM:229300; Friedreich ataxia 1 MONDO:0100340
White matter disorders and cerebral calcification - narrow panel v1.60 TMEM63A Ivone Leong Phenotypes for gene: TMEM63A were changed from Leukodystrophy, hypomyelinating, 19, transient infantile, MIM# 618688 to Leukodystrophy, hypomyelinating, 19, transient infantile, OMIM:618688
Paediatric disorders - additional genes v1.93 CTU2 Ivone Leong Entity copied from Severe microcephaly v2.146
Paediatric disorders - additional genes v1.93 CTU2 Ivone Leong gene: CTU2 was added
gene: CTU2 was added to Paediatric disorders - additional genes. Sources: Expert Review Amber,Expert list
Q2_21_rating tags were added to gene: CTU2.
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to 26633546; 27480277; 31301155
Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, OMIM:618142
Disorders of sex development v2.47 CTU2 Ivone Leong Entity copied from Severe microcephaly v2.146
Disorders of sex development v2.47 CTU2 Ivone Leong gene: CTU2 was added
gene: CTU2 was added to Disorders of sex development. Sources: Expert Review Amber,Expert list
Q2_21_rating tags were added to gene: CTU2.
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to 26633546; 27480277; 31301155
Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, OMIM:618142
Intellectual disability v3.1066 UBTF Arina Puzriakova Phenotypes for gene: UBTF were changed from developmental regression; motor and language regression; developmental delay; Neurodegeneration, childhood-onset, with brain atrophy, 617672 to Neurodegeneration, childhood-onset, with brain atrophy, OMIM:617672
Ataxia and cerebellar anomalies - narrow panel v2.158 UBTF Arina Puzriakova Phenotypes for gene: UBTF were changed from Neurodegeneration, childhood-onset, with brain atrophy MIM#617672 to Neurodegeneration, childhood-onset, with brain atrophy, OMIM:617672
Childhood onset dystonia or chorea or related movement disorder v1.97 UBTF Arina Puzriakova Phenotypes for gene: UBTF were changed from Neurodegeneration, childhood-onset, with brain atrophy MIM#617672 to Neurodegeneration, childhood-onset, with brain atrophy, OMIM:617672
Intellectual disability v3.1065 DYNC1I2 Arina Puzriakova Phenotypes for gene: DYNC1I2 were changed from Abnormality of nervous system morphology; Abnormality of head or neck; Microcephaly; Intellectual disability to Neurodevelopmental disorder with microcephaly and structural brain anomalies, OMIM:618492
Severe microcephaly v2.146 CTU2 Ivone Leong Tag Q2_21_rating tag was added to gene: CTU2.
Severe microcephaly v2.146 CTU2 Ivone Leong Classified gene: CTU2 as Amber List (moderate evidence)
Severe microcephaly v2.146 CTU2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype.

PMID:26633546. Affected members of all 3 families have microcephaly, facial dysmorphia and unilateral renal agenesis. 2/3 families have ambiguous genitalia; however, only 1 family had karyotyping done, which showed normal male karyotype (46 XY). 2/3 had congenital heart disease.

PMID: 27480277. Same variant as PMID:26633546. Affected individuals in this extended family have similar phenotype as PMID:26633546. Patient 1: in addition to microcephaly also has renal anomalies (small kidneys) and possible ambiguous genitalia with normal XY karyotype. Patient 2: cousin of patient 1. In addition to microcephaly did not have renal anomalies and nor ambiguous genitalia. Both patients have congenital heart disease.

PMID: 31301155. 5 new cases, all with microcephaly. 4/5 with renal anomalies, 2/5 with ambiguous genitalia, 4/5 congenital heart disease.

There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Severe microcephaly v2.146 CTU2 Ivone Leong Gene: ctu2 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.145 DYNC1I2 Arina Puzriakova Phenotypes for gene: DYNC1I2 were changed from Neurodevelopmental disorder with microcephaly and structural brain anomalies , MIM#618492 to Neurodevelopmental disorder with microcephaly and structural brain anomalies, OMIM:618492
Growth failure in early childhood v1.67 DNA2 Arina Puzriakova Publications for gene: DNA2 were set to PMC3912419
Growth failure in early childhood v1.66 DNA2 Arina Puzriakova commented on gene: DNA2
Growth failure in early childhood v1.66 DNA2 Arina Puzriakova Phenotypes for gene: DNA2 were changed from seckel syndrome to Seckel syndrome 8, OMIM:615807
Cerebral vascular malformations v2.51 DNA2 Arina Puzriakova Phenotypes for gene: DNA2 were changed from Seckel syndrome 8 615807 to Seckel syndrome 8, OMIM:615807
Intellectual disability v3.1064 DNA2 Arina Puzriakova reviewed gene: DNA2: Rating: RED; Mode of pathogenicity: None; Publications: 24389050, 31045292; Phenotypes: Seckel syndrome 8, OMIM:615807; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v2.144 DNA2 Arina Puzriakova Publications for gene: DNA2 were set to 24389050; 31045292
Intellectual disability v3.1064 DNA2 Arina Puzriakova Publications for gene: DNA2 were set to 23352259; 24389050
Intellectual disability v3.1063 DNA2 Arina Puzriakova Phenotypes for gene: DNA2 were changed from PRIMORDIAL DWARFISM SECKEL SYNDROME 8; SCKL8 to Seckel syndrome 8, OMIM:615807
Severe microcephaly v2.143 DNA2 Arina Puzriakova Phenotypes for gene: DNA2 were changed from Seckel syndrome 8, OMIM:615807 to Seckel syndrome 8, OMIM:615807; Microcephalic primordial dwarfism, MONDO:0017950
Severe microcephaly v2.142 DNA2 Arina Puzriakova Tag Q2_21_rating tag was added to gene: DNA2.
Severe microcephaly v2.142 DNA2 Arina Puzriakova Classified gene: DNA2 as Amber List (moderate evidence)
Severe microcephaly v2.142 DNA2 Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber but there is sufficient evidence to promote this gene to Green at the next GMS panel update - 4 different homozygous variants identified in at least 5 unrelated families with microcephalic primordial dwarfism (PMIDs: 24389050; 31045292)
Severe microcephaly v2.142 DNA2 Arina Puzriakova Gene: dna2 has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v2.131 WFS1 Eleanor Williams Added comment: Comment on phenotypes: Previous phenotypes were: Diabetes with additional phenotypes suggestive of a monogenic aetiology;Inherited optic neuropathies;Wolfram syndrome 1, 222300;Mitochondrial respiratory chain disorders caused by nuclear variants only;Hereditary ataxia;Familial diabetes;Congenital hearing impairment (profound/severe)
Inborn errors of metabolism v2.131 WFS1 Eleanor Williams Phenotypes for gene: WFS1 were changed from Diabetes with additional phenotypes suggestive of a monogenic aetiology; Inherited optic neuropathies; Wolfram syndrome 1, 222300; Mitochondrial respiratory chain disorders caused by nuclear variants only; Hereditary ataxia; Familial diabetes; Congenital hearing impairment (profound/severe) to Wolfram syndrome 1, OMIM:222300; Wolfram-like syndrome, autosomal dominant, OMIM:614296; Diabetes mellitus, noninsulin-dependent, association with, OMIM:125853
Inborn errors of metabolism v2.130 WFS1 Eleanor Williams Publications for gene: WFS1 were set to 27604308; 30171196
Inborn errors of metabolism v2.129 WFS1 Eleanor Williams reviewed gene: WFS1: Rating: ; Mode of pathogenicity: None; Publications: 33693650; Phenotypes: ; Mode of inheritance: None
Undiagnosed metabolic disorders v1.457 WFS1 Eleanor Williams Added comment: Comment on phenotypes: Original phenotypes were: Wolfram syndrome 1 (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Congenital hearing impairment (profound/severe); Diabetes with additional phenotypes suggestive of a monogenic aetiology; Familial diabetes; Hereditary ataxia; Inherited optic neuropathies.
Undiagnosed metabolic disorders v1.457 WFS1 Eleanor Williams Phenotypes for gene: WFS1 were changed from Wolfram syndrome 1 (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Congenital hearing impairment (profound/severe); Diabetes with additional phenotypes suggestive of a monogenic aetiology; Familial diabetes; Hereditary ataxia; Inherited optic neuropathies to Wolfram syndrome 1, OMIM:222300
Undiagnosed metabolic disorders v1.456 WFS1 Eleanor Williams reviewed gene: WFS1: Rating: ; Mode of pathogenicity: None; Publications: 33693650; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.157 WFS1 Eleanor Williams Phenotypes for gene: WFS1 were changed from Wolfram syndrome 1, 222300 to Wolfram syndrome 1, OMIM:222300
Ataxia and cerebellar anomalies - narrow panel v2.156 WFS1 Eleanor Williams reviewed gene: WFS1: Rating: ; Mode of pathogenicity: None; Publications: 33693650; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v2.141 DNA2 Arina Puzriakova Publications for gene: DNA2 were set to 24389050
Severe microcephaly v2.140 DNA2 Arina Puzriakova Phenotypes for gene: DNA2 were changed from ?Seckel syndrome 8, 615807; SCKL8 to Seckel syndrome 8, OMIM:615807
Severe microcephaly v2.139 CTU2 Ivone Leong Publications for gene: CTU2 were set to 26633546
Severe microcephaly v2.138 CTU2 Ivone Leong Phenotypes for gene: CTU2 were changed from Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome (MIM#618142) to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, OMIM:618142
Severe microcephaly v2.137 CTCF Ivone Leong Classified gene: CTCF as Amber List (moderate evidence)
Severe microcephaly v2.137 CTCF Ivone Leong Gene: ctcf has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.136 CTCF Ivone Leong gene: CTCF was added
gene: CTCF was added to Severe microcephaly. Sources: Expert list
Q2_21_rating tags were added to gene: CTCF.
Mode of inheritance for gene: CTCF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CTCF were set to 23746550; 30893510; 28619046
Phenotypes for gene: CTCF were set to Mental retardation, autosomal dominant 21, OMIM:615502
Review for gene: CTCF was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. New gene added by Zornitza Stark (however, it was added under the gene symbol CTSF but should be CTCF) with the following review:

"Recommended gene rating: Green
PMID: 23746550
- 4 probands, 2x PTV, 1x missense, 1x 280kb deletion (all de novo)
- OFCs ranges from -0.8 SD (the proband with the deletion) to -3.51 SD

PMID: 30893510
- 3 probands, de novo 2x PTV and 1x missense
- OFCs ranges from < -2 to < -3 SD

PMID: 28619046
- 1x proband with de novo fs
- head circumference was under 10th centle
Sources: Expert list
Created: 4 Sep 2020, 10:18 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Mental retardation, autosomal dominant 21 (MIM#615502)

Publications

23746550
30893510
28619046

Variants in this GENE are reported as part of current diagnostic practice
Created: 4 Sep 2020, 10:18 a.m."

There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Sources: Expert list
Severe microcephaly v2.135 CTSF Ivone Leong edited their review of gene: CTSF: Added comment: This gene has been tagged with "curated_removed" as it should be CTCF not CTSF gene added to this panel.; Changed rating: RED
Severe microcephaly v2.135 CTSF Ivone Leong Tag curated_removed tag was added to gene: CTSF.
Severe microcephaly v2.135 CTSF Ivone Leong changed review comment from: Comment on phenotypes: CTSF is no longer associated with Mental retardation, autosomal dominant 21, OMIM:615502 on OMIM.; to: Comment on phenotypes: CTSF is not associated with Mental retardation, autosomal dominant 21, OMIM:615502 on OMIM.
Severe microcephaly v2.135 CTSF Ivone Leong Added comment: Comment on phenotypes: CTSF is no longer associated with Mental retardation, autosomal dominant 21, OMIM:615502 on OMIM.
Severe microcephaly v2.135 CTSF Ivone Leong Phenotypes for gene: CTSF were changed from Mental retardation, autosomal dominant 21, OMIM:615502 to Ceroid lipofuscinosis, neuronal, 13, Kufs type, OMIM:615362
Severe microcephaly v2.134 CTSF Ivone Leong Phenotypes for gene: CTSF were changed from Mental retardation, autosomal dominant 21 (MIM#615502) to Mental retardation, autosomal dominant 21, OMIM:615502
Optic neuropathy v2.40 WFS1 Eleanor Williams Phenotypes for gene: WFS1 were changed from Wolfram syndrome to Wolfram syndrome 1, OMIM:222300
Optic neuropathy v2.39 WFS1 Eleanor Williams Publications for gene: WFS1 were set to
Optic neuropathy v2.38 WFS1 Eleanor Williams reviewed gene: WFS1: Rating: ; Mode of pathogenicity: None; Publications: 33693650; Phenotypes: ; Mode of inheritance: None
Monogenic diabetes v2.42 WFS1 Eleanor Williams Publications for gene: WFS1 were set to 27217304; 27185633
Monogenic diabetes v2.41 WFS1 Eleanor Williams reviewed gene: WFS1: Rating: ; Mode of pathogenicity: None; Publications: 33693650; Phenotypes: ; Mode of inheritance: None
Familial diabetes v1.61 WFS1 Eleanor Williams Phenotypes for gene: WFS1 were changed from Wolfram syndrome, 222300 to Wolfram syndrome, OMIM:222300
Familial diabetes v1.60 WFS1 Eleanor Williams Publications for gene: WFS1 were set to 27217304; 27185633
Familial diabetes v1.59 WFS1 Eleanor Williams reviewed gene: WFS1: Rating: ; Mode of pathogenicity: None; Publications: 33693650; Phenotypes: ; Mode of inheritance: None
Diabetes with additional phenotypes suggestive of a monogenic aetiology v1.62 WFS1 Eleanor Williams Phenotypes for gene: WFS1 were changed from Wolfram syndrome, 222300; Deafness, autosomal dominant 6/14/38, 600965; Wolfram-like syndrome, autosomal dominant, 614296; {Diabetes mellitus, noninsulin-dependent, association with}, 125853; ?Cataract 41,116400; Deafness,autosomal dominant 6/14/38, 600965; Wolfram syndrome, 222300; {Diabetes mellitus, noninsulin-dependent,association with}; diabetes insipidus or optic atrophy to Wolfram syndrome, OMIM:222300; Deafness, autosomal dominant 6/14/38, OMIM:600965; Wolfram-like syndrome, autosomal dominant, OMIM:614296; {Diabetes mellitus, noninsulin-dependent, association with}, OMIM:125853; ?Cataract 41, OMIM:116400; diabetes insipidus or optic atrophy
Diabetes with additional phenotypes suggestive of a monogenic aetiology v1.61 WFS1 Eleanor Williams Publications for gene: WFS1 were set to 27217304; 27185633
Diabetes with additional phenotypes suggestive of a monogenic aetiology v1.60 WFS1 Eleanor Williams commented on gene: WFS1
Neurodegenerative disorders - adult onset v2.174 SNCB Eleanor Williams reviewed gene: SNCB: Rating: AMBER; Mode of pathogenicity: None; Publications: 33760043, 15365127, 12641375; Phenotypes: Dementia, Lewy body, OMIM:127750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.48 SNCB Eleanor Williams reviewed gene: SNCB: Rating: AMBER; Mode of pathogenicity: None; Publications: 33760043, 15365127, 12641375; Phenotypes: Dementia, Lewy body, OMIM:127750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Lipodystrophy - childhood onset v2.12 OTULIN Ivone Leong Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099 to Autoinflammation, panniculitis, and dermatosis syndrome, OMIM:617099
Lipodystrophy - childhood onset v2.11 FBN1 Ivone Leong Phenotypes for gene: FBN1 were changed from Marfan lipodystrophy syndrome, MIM# 616914 to Marfan lipodystrophy syndrome, OMIM:616914
Lipodystrophy - childhood onset v2.10 KCNJ6 Ivone Leong Phenotypes for gene: KCNJ6 were changed from Keppen-Lubinsky syndrome, MIM# 614098; MONDO:0013572 to Keppen-Lubinsky syndrome, OMIM:614098; Keppen-Lubinsky syndrome, MONDO:0013572
Familial pulmonary fibrosis v1.15 ZCCHC8 Ivone Leong Tag watchlist tag was added to gene: ZCCHC8.
Familial pulmonary fibrosis v1.15 ZCCHC8 Ivone Leong Classified gene: ZCCHC8 as Amber List (moderate evidence)
Familial pulmonary fibrosis v1.15 ZCCHC8 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Familial pulmonary fibrosis v1.15 ZCCHC8 Ivone Leong Gene: zcchc8 has been classified as Amber List (Moderate Evidence).
Familial pulmonary fibrosis v1.14 ZCCHC8 Ivone Leong Phenotypes for gene: ZCCHC8 were changed from Pulmonary fibrosis to ?Pulmonary fibrosis and/or bone marrow failure, telomere-related, 5, OMIM:618674
Primary lymphoedema v2.12 ARAP3 Ivone Leong Classified gene: ARAP3 as Amber List (moderate evidence)
Primary lymphoedema v2.12 ARAP3 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Primary lymphoedema v2.12 ARAP3 Ivone Leong Gene: arap3 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v2.11 ARAP3 Ivone Leong Tag watchlist tag was added to gene: ARAP3.
Primary lymphoedema v2.11 RORC Ivone Leong Classified gene: RORC as Amber List (moderate evidence)
Primary lymphoedema v2.11 RORC Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been rated Amber.
Primary lymphoedema v2.11 RORC Ivone Leong Gene: rorc has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v2.10 RORC Ivone Leong Tag watchlist tag was added to gene: RORC.
Severe microcephaly v2.133 CSNK2A1 Ivone Leong Classified gene: CSNK2A1 as Amber List (moderate evidence)
Severe microcephaly v2.133 CSNK2A1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Severe microcephaly v2.133 CSNK2A1 Ivone Leong Gene: csnk2a1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.132 CSNK2A1 Ivone Leong Tag Q2_21_rating tag was added to gene: CSNK2A1.
Severe microcephaly v2.132 CSNK2A1 Ivone Leong Phenotypes for gene: CSNK2A1 were changed from Okur-Chung neurodevelopmental syndrome MIM#617062 to Okur-Chung neurodevelopmental syndrome, OMIM:617062
Severe microcephaly v2.131 CHAMP1 Ivone Leong Classified gene: CHAMP1 as Amber List (moderate evidence)
Severe microcephaly v2.131 CHAMP1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Severe microcephaly v2.131 CHAMP1 Ivone Leong Gene: champ1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.130 CHAMP1 Ivone Leong Tag Q2_21_rating tag was added to gene: CHAMP1.
Severe microcephaly v2.130 CHAMP1 Ivone Leong Added comment: Comment on publications: PMID: 26751395 additional paper
Severe microcephaly v2.130 CHAMP1 Ivone Leong Publications for gene: CHAMP1 were set to 27148580; 26340335
Severe microcephaly v2.129 CHAMP1 Ivone Leong Phenotypes for gene: CHAMP1 were changed from Mental retardation, autosomal dominant 40 (MIM#616579) to Mental retardation, autosomal dominant 40, OMIM:616579
Severe microcephaly v2.128 CEP63 Ivone Leong commented on gene: CEP63
Severe microcephaly v2.128 CEP63 Ivone Leong Tag Q2_21_expert_review tag was added to gene: CEP63.
Severe microcephaly v2.128 CEP57 Ivone Leong Classified gene: CEP57 as Amber List (moderate evidence)
Severe microcephaly v2.128 CEP57 Ivone Leong Gene: cep57 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.127 CEP57 Ivone Leong gene: CEP57 was added
gene: CEP57 was added to Severe microcephaly. Sources: Literature
Q2_21_rating tags were added to gene: CEP57.
Mode of inheritance for gene: CEP57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP57 were set to 24259107; 30010053; 21552266
Phenotypes for gene: CEP57 were set to Mosaic variegated aneuploidy syndrome 2, OMIM:614114
Review for gene: CEP57 was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There are 7 reported cases (9 affected individuals) with homozygous/compound heterzygous variants in this gene (4 variants - c.520_521delGA, c.915_925dup11, c241C>T, c.697delA). Microcephaly is reported in 5/9 individuals (4 families - in 1 family with 2 affected sibs only 1 sib had microcephaly). Those with microcephaly are either compound heterozygous or homozygous for c.915_925dup11 (Mexican, Caucasian, Moroccan origin). There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Sources: Literature
Severe microcephaly v2.126 TRIP13 Ivone Leong Classified gene: TRIP13 as Amber List (moderate evidence)
Severe microcephaly v2.126 TRIP13 Ivone Leong Gene: trip13 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.125 TRIP13 Ivone Leong gene: TRIP13 was added
gene: TRIP13 was added to Severe microcephaly. Sources: Literature
watchlist tags were added to gene: TRIP13.
Mode of inheritance for gene: TRIP13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIP13 were set to 28553959
Phenotypes for gene: TRIP13 were set to Mosaic variegated aneuploidy syndrome 3, OMIM:617598
Review for gene: TRIP13 was set to AMBER
Added comment: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. PMID: 28553959 describes 6 probands with variants in this gene. 3/6 probands had microcephaly (2 of these probands have the same homozygous variant and may be due to a founder effect). Therefore, there is currently not enough evidence to support a gene-disease association. This gene has been rated Amber for now.
Sources: Literature
Severe microcephaly v2.124 BUB1B Ivone Leong Classified gene: BUB1B as Amber List (moderate evidence)
Severe microcephaly v2.124 BUB1B Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is enough evidence to support gene-disease association. This gene should be rated Green at the next review.
Severe microcephaly v2.124 BUB1B Ivone Leong Gene: bub1b has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.123 BUB1B Ivone Leong Tag Q2_21_rating tag was added to gene: BUB1B.
Severe microcephaly v2.123 BUB1B Ivone Leong Phenotypes for gene: BUB1B were changed from Mosaic variegated aneuploidy syndrome 1 (MIM#257300) to Mosaic variegated aneuploidy syndrome 1, OMIM:257300
Severe microcephaly v2.122 BPTF Ivone Leong Classified gene: BPTF as Amber List (moderate evidence)
Severe microcephaly v2.122 BPTF Ivone Leong Added comment: Comment on list classification: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support gene-diseas association. This gene should be rated Green at the next review.
Severe microcephaly v2.122 BPTF Ivone Leong Gene: bptf has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.121 BPTF Ivone Leong Tag Q2_21_rating tag was added to gene: BPTF.
Severe microcephaly v2.121 BPTF Ivone Leong Added comment: Comment on publications: PMID:33522091 additonal paper describing 12/20 unrelated cases with microcephaly
Severe microcephaly v2.121 BPTF Ivone Leong Publications for gene: BPTF were set to 28942966
Severe microcephaly v2.120 BPTF Ivone Leong Phenotypes for gene: BPTF were changed from Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, MIM# 617755 to Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, OMIM:617755
White matter disorders and cerebral calcification - narrow panel v1.59 AARS Ivone Leong commented on gene: AARS: Added new-gene-name tag, new approved HGNC gene symbol for AARS is AARS1
White matter disorders and cerebral calcification - narrow panel v1.59 AARS Ivone Leong Tag new-gene-name tag was added to gene: AARS.
Severe microcephaly v2.119 AARS Ivone Leong Tag Q2_21_rating tag was added to gene: AARS.
White matter disorders and cerebral calcification - narrow panel v1.59 AARS Ivone Leong Classified gene: AARS as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.59 AARS Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant disorder in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
White matter disorders and cerebral calcification - narrow panel v1.59 AARS Ivone Leong Gene: aars has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v1.58 AARS Ivone Leong Tag Q2_21_rating tag was added to gene: AARS.
Severe microcephaly v2.119 AARS Ivone Leong Classified gene: AARS as Amber List (moderate evidence)
Severe microcephaly v2.119 AARS Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant disorder in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Severe microcephaly v2.119 AARS Ivone Leong Gene: aars has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.118 AARS Ivone Leong commented on gene: AARS
Severe microcephaly v2.118 AARS Ivone Leong Tag new-gene-name tag was added to gene: AARS.
Intellectual disability v3.1062 WDR4 Ivone Leong reviewed gene: WDR4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.1062 WDR4 Ivone Leong Phenotypes for gene: WDR4 were changed from Primordial dwarfism; motor and speech delay; intellectual disability; global developmental delay. to Galloway-Mowat syndrome 6, OMIM:61834; Microcephaly, growth deficiency, seizures, and brain malformations, OMIM:618347
Intellectual disability v3.1061 WDR4 Ivone Leong Tag Q2_21_rating tag was added to gene: WDR4.
Intellectual disability v3.1061 WDR4 Ivone Leong Publications for gene: WDR4 were set to 29597095; 26416026
Severe microcephaly v2.118 WDR4 Ivone Leong reviewed gene: WDR4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v2.118 WDR4 Ivone Leong Tag Q2_21_rating tag was added to gene: WDR4.
Severe microcephaly v2.118 WDR4 Ivone Leong Publications for gene: WDR4 were set to 26416026; 29597095; 30079490; 29597095
Primary immunodeficiency v2.419 IL6ST Eleanor Williams reviewed gene: IL6ST: Rating: ; Mode of pathogenicity: None; Publications: 33517393; Phenotypes: ; Mode of inheritance: None
Unexplained paediatric onset end-stage renal disease v1.18 OCRL Eleanor Williams Publications for gene: OCRL were set to 21249396; 17384968
Unexplained paediatric onset end-stage renal disease v1.17 OCRL Eleanor Williams Phenotypes for gene: OCRL were changed from LOWE OCULOCEREBRORENAL SYNDROME #309000; Dent disease 2 #300555 to Lowe syndrome, OMIM:309000; Dent disease 2, OMIM:300555
Unexplained paediatric onset end-stage renal disease v1.16 OCRL Eleanor Williams edited their review of gene: OCRL: Added comment: Genotype/Phenotype information: PMID: 33517444 - Ramadesikan et al 2021 - studied the cellular effect of 7 OCRL1 (OCRL) variants identified in Lowe Syndrome patients in kidney epithelial cells. Differences in cell spreading, ciliogenesis, protein localization and degree of Golgi apparatus fragmentation were observed. The results help provide a framework to explain symptom heterogeneity and may help stratify patients; Changed publications: 33517444
Undiagnosed metabolic disorders v1.456 OCRL Eleanor Williams Phenotypes for gene: OCRL were changed from Dent disease 2 300555; Lowe syndrome 309000 to Dent disease 2, OMIM:300555; Lowe syndrome, OMIM:309000
Undiagnosed metabolic disorders v1.455 OCRL Eleanor Williams Publications for gene: OCRL were set to 27604308; 8504307; 9632163; 9632163; 15627218; 27625797
Undiagnosed metabolic disorders v1.454 OCRL Eleanor Williams reviewed gene: OCRL: Rating: ; Mode of pathogenicity: None; Publications: 33517444; Phenotypes: ; Mode of inheritance: None
Inborn errors of metabolism v2.129 OCRL Eleanor Williams Publications for gene: OCRL were set to 27604308; 8504307; 9632163; 9632163; 15627218; 27625797
Inborn errors of metabolism v2.128 OCRL Eleanor Williams Phenotypes for gene: OCRL were changed from Dent disease 2 300555; Lowe syndrome 309000 to Dent disease 2, OMIM:300555; Lowe syndrome, OMIM:309000
Inborn errors of metabolism v2.127 OCRL Eleanor Williams reviewed gene: OCRL: Rating: ; Mode of pathogenicity: None; Publications: 33517444; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v1.648 OCRL Eleanor Williams Phenotypes for gene: OCRL were changed from DENT DISEASE TYPE 2; LOWE OCULOCEREBRORENAL SYNDROME to Dent disease 2, OMIM:300555; Lowe syndrome, OMIM:309000
Fetal anomalies v1.647 OCRL Eleanor Williams Publications for gene: OCRL were set to
Fetal anomalies v1.646 OCRL Eleanor Williams reviewed gene: OCRL: Rating: ; Mode of pathogenicity: None; Publications: 33517444; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.1060 OCRL Eleanor Williams Publications for gene: OCRL were set to
Intellectual disability v3.1059 OCRL Eleanor Williams reviewed gene: OCRL: Rating: ; Mode of pathogenicity: None; Publications: 33517444; Phenotypes: ; Mode of inheritance: None
Proteinuric renal disease v2.50 OCRL Eleanor Williams Phenotypes for gene: OCRL were changed from LOWE OCULOCEREBRORENAL SYNDROME #309000; Dent disease 2 #300555 to Lowe syndrome, OMIM:309000; Dent disease 2, OMIM:300555
Childhood onset dystonia or chorea or related movement disorder v1.96 FITM2 Sarah Leigh edited their review of gene: FITM2: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least four variants reported in at least three unrelated cases. Supportive drosophila model.; Changed rating: GREEN
Proteinuric renal disease v2.49 OCRL Eleanor Williams commented on gene: OCRL: Genotype/Phenotype information: PMID: 33517444 - Ramadesikan et al 2021 - studied the cellular effect of 7 OCRL1 (OCRL) variants identified in Lowe Syndrome patients in kidney epithelial cells. Differences in cell spreading, ciliogenesis, protein localization and degree of Golgi apparatus fragmentation were observed. The results help provide a framework to explains symptom heterogeneity and may help stratify patients.
White matter disorders - adult onset v1.10 OCRL Eleanor Williams Phenotypes for gene: OCRL were changed from Lowe syndrome, 309000 to Lowe syndrome, OMIM:309000
White matter disorders - adult onset v1.9 OCRL Eleanor Williams Publications for gene: OCRL were set to 27159321; 25527826; 28334938; 20301621; 24357685
White matter disorders - adult onset v1.8 OCRL Eleanor Williams reviewed gene: OCRL: Rating: ; Mode of pathogenicity: None; Publications: 33517444; Phenotypes: ; Mode of inheritance: None
Cataracts v2.74 OCRL Eleanor Williams Phenotypes for gene: OCRL were changed from Lowe syndrome; Confirmed DD gene for LOWE OCULOCEREBRORENAL SYNDROME to Lowe syndrome, OMIM:309000; Confirmed DD gene for LOWE OCULOCEREBRORENAL SYNDROME
Childhood onset dystonia or chorea or related movement disorder v1.96 FITM2 Sarah Leigh Tag Q2_21_rating tag was added to gene: FITM2.
Childhood onset dystonia or chorea or related movement disorder v1.96 FITM2 Sarah Leigh Classified gene: FITM2 as Amber List (moderate evidence)
Childhood onset dystonia or chorea or related movement disorder v1.96 FITM2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia or chorea or related movement disorder v1.96 FITM2 Sarah Leigh Gene: fitm2 has been classified as Amber List (Moderate Evidence).
Cataracts v2.73 OCRL Eleanor Williams Publications for gene: OCRL were set to
Cataracts v2.72 OCRL Eleanor Williams reviewed gene: OCRL: Rating: ; Mode of pathogenicity: None; Publications: 33517444; Phenotypes: ; Mode of inheritance: None
Nephrocalcinosis or nephrolithiasis v2.18 OCRL Eleanor Williams Phenotypes for gene: OCRL were changed from Lowe syndrome, 309000; Dent disease 2, 300555; As for CLCN5 (Nephrocalcinosis with low molecular weight proteinuria and pregressive CKD) but may include intellectual disability and other features of Lowe syndrome to Lowe syndrome, OMIM:309000; Dent disease 2, OMIM:300555; As for CLCN5 (Nephrocalcinosis with low molecular weight proteinuria and pregressive CKD) but may include intellectual disability and other features of Lowe syndrome
Nephrocalcinosis or nephrolithiasis v2.17 OCRL Eleanor Williams Publications for gene: OCRL were set to
Nephrocalcinosis or nephrolithiasis v2.16 OCRL Eleanor Williams reviewed gene: OCRL: Rating: ; Mode of pathogenicity: None; Publications: 33517444; Phenotypes: ; Mode of inheritance: None
Glaucoma (developmental) v1.35 OCRL Eleanor Williams Publications for gene: OCRL were set to 19168822
Glaucoma (developmental) v1.34 OCRL Eleanor Williams reviewed gene: OCRL: Rating: ; Mode of pathogenicity: None; Publications: 33517444; Phenotypes: ; Mode of inheritance: None
Childhood onset dystonia or chorea or related movement disorder v1.95 FITM2 Sarah Leigh Phenotypes for gene: FITM2 were changed from Siddiqi syndrome MIM#618635; dystonia; deafness to Siddiqi syndrome OMIM:618635; siddiqi syndrome MONDO:0032842
Childhood onset dystonia or chorea or related movement disorder v1.94 SCN1A Sarah Leigh Tag Q2_21_phenotype tag was added to gene: SCN1A.
Childhood onset dystonia or chorea or related movement disorder v1.94 SCN1A Sarah Leigh edited their review of gene: SCN1A: Added comment: A non-Dravet syndrome epileptic encephalopathy phenotype associated with SCN1A variants. Eight cases carriers of p.Thr226Met shared this non-typical phenotype. This phenotype is not represented in OMIM, but they have been notified of the reporting publication (PMID 28794249), additional phenotype may be added to OMIM in the future.; Changed rating: GREEN
Primary lymphoedema v2.10 RORC Ivone Leong Phenotypes for gene: RORC were changed from Lymphoedema to Lymphoedema, MONDO:0019297
Primary lymphoedema v2.9 ARAP3 Ivone Leong Phenotypes for gene: ARAP3 were changed from Lymphoedema to Lymphoedema, MONDO:0019297
Retinal disorders v2.185 FAM57B Ivone Leong Classified gene: FAM57B as Amber List (moderate evidence)
Retinal disorders v2.185 FAM57B Ivone Leong Added comment: Comment on list classification: This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Retinal disorders v2.185 FAM57B Ivone Leong Gene: fam57b has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia or chorea or related movement disorder v1.94 SCN1A Sarah Leigh Classified gene: SCN1A as Amber List (moderate evidence)
Childhood onset dystonia or chorea or related movement disorder v1.94 SCN1A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia or chorea or related movement disorder v1.94 SCN1A Sarah Leigh Gene: scn1a has been classified as Amber List (Moderate Evidence).
Retinal disorders v2.184 FAM57B Ivone Leong Tag Q2_21_rating tag was added to gene: FAM57B.
Childhood onset dystonia or chorea or related movement disorder v1.93 SCN1A Sarah Leigh Publications for gene: SCN1A were set to 19332696; 16054936
Intellectual disability v3.1059 CDH11 Arina Puzriakova Phenotypes for gene: CDH11 were changed from Elsahy-Waters syndrome to Elsahy-Waters syndrome, OMIM:211380; Teebi hypertelorism syndrome
Intellectual disability v3.1058 CDH11 Arina Puzriakova Publications for gene: CDH11 were set to 27431290; 29271567
Ataxia and cerebellar anomalies - narrow panel v2.156 SCN1A Sarah Leigh edited their review of gene: SCN1A: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported in unrelated cases.; Changed rating: GREEN
Intellectual disability v3.1057 CDH11 Arina Puzriakova Added comment: Comment on mode of inheritance: Association with biallelic variants well-established, with ID reported in all cases to date. On the other hand, DD/ID is variable in individuals with monoallelic variants (PMID: 33811546) - 7/19 cases (4 families) presented a developmental phenotype including very mild speech delays in 5/7, mild-moderate DD in 1/7, and global delay in 1/7 individuals.

Overall, given the mostly mild degree of cognitive delay, as well as intra- and interfamilial reduced penetrance of this feature, there is currently not enough evidence to rate as Green on this panel for the monoallelic disease.
Intellectual disability v3.1057 CDH11 Arina Puzriakova Mode of inheritance for gene: CDH11 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.156 SCN1A Sarah Leigh Tag Q2_21_rating tag was added to gene: SCN1A.
Ataxia and cerebellar anomalies - narrow panel v2.156 SCN1A Sarah Leigh Publications for gene: SCN1A were set to 27264139; 27817982; 28732259
Ataxia and cerebellar anomalies - narrow panel v2.155 SCN1A Sarah Leigh Classified gene: SCN1A as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.155 SCN1A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.155 SCN1A Sarah Leigh Gene: scn1a has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.117 WDR4 Ivone Leong Publications for gene: WDR4 were set to 26416026; 29597095
Severe microcephaly v2.116 WDR4 Ivone Leong Phenotypes for gene: WDR4 were changed from MPD; microcephalic primordial dwarfism to Galloway-Mowat syndrome 6, OMIM:61834; Microcephaly, growth deficiency, seizures, and brain malformations, OMIM:618347
Severe microcephaly v2.115 WDR37 Ivone Leong Classified gene: WDR37 as Amber List (moderate evidence)
Severe microcephaly v2.115 WDR37 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support this gene-disease association. This gene should be rated Green at the next review.
Severe microcephaly v2.115 WDR37 Ivone Leong Gene: wdr37 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.114 WDR37 Ivone Leong Tag Q2_21_rating tag was added to gene: WDR37.
Ataxia and cerebellar anomalies - narrow panel v2.154 SCN1A Sarah Leigh Phenotypes for gene: SCN1A were changed from Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208 to Dravet syndrome OMIM:607208; developmental and epileptic encephalopathy, 6 MONDO:0100079
Severe microcephaly v2.114 WDR37 Ivone Leong Phenotypes for gene: WDR37 were changed from Neurooculocardiogenitourinary syndrome MIM#618652 to Neurooculocardiogenitourinary syndrome, OMIM:618652
Proteinuric renal disease v2.49 APOL1 Eleanor Williams Publications for gene: APOL1 were set to 20647424; 23766536
Proteinuric renal disease v2.48 APOL1 Eleanor Williams edited their review of gene: APOL1: Added comment: PMID: 33517446 - Ge et al 2021 - demonstrate a mouse model to study APOL1 risk variants associated susceptibility to NFAT-mediated FSGS. They provide evidence that APOL1 G1 induced glomerular lipid accumulation correlates with loss of renal function and confirm that APOL1 G1/G2 risk variant is associated with mitochondrial dysfunction.; Changed publications: 33517446
Genetic epilepsy syndromes v2.339 UFSP2 Sarah Leigh Classified gene: UFSP2 as Amber List (moderate evidence)
Genetic epilepsy syndromes v2.339 UFSP2 Sarah Leigh Gene: ufsp2 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v2.338 UFSP2 Sarah Leigh Tag Q2_21_rating was removed from gene: UFSP2.
Tag founder-effect tag was added to gene: UFSP2.
Genetic epilepsy syndromes v2.338 UFSP2 Sarah Leigh Publications for gene: UFSP2 were set to 33473208; 28892125; 26428751; 32755715
Genetic epilepsy syndromes v2.337 UFSP2 Sarah Leigh Classified gene: UFSP2 as Green List (high evidence)
Genetic epilepsy syndromes v2.337 UFSP2 Sarah Leigh Added comment: Comment on list classification: A founder variant (rs142500730) reported in four South Asian families (haplotype analysis available for two of the families proves relatedness). Functional studies suggest that although expression seems to be unaffected, immunoblotting indicates that protein stability maybe affected (PMID 33473208).
Genetic epilepsy syndromes v2.337 UFSP2 Sarah Leigh Gene: ufsp2 has been classified as Green List (High Evidence).
Intellectual disability v3.1056 HTT Eleanor Williams changed review comment from: PMID: 33432339 - Jung et al 2021 - further characterisation of the family previously reported in PMID: 27329733 (Rodan et al 2016) - using WGS they confirm they are the most likely cause of the LOMARS phenotype and clarify their locations as NM_002111.8(HTT): c.8157T>A (p.Phe2719Leu) and NM_002111.8(HTT)c.4469+1G>A (Note there are incorrect Clinvar entries). Functional studies show them each to be a hypomorphic mutation, resulting in severe deficiency of huntingtin in compound heterozygotes.; to: PMID: 33432339 - Jung et al 2021 - further characterisation of the family previously reported in PMID: 27329733 (Rodan et al 2016) - using WGS they confirm they are the most likely cause of the LOMARS phenotype and clarify their locations as NM_002111.8(HTT): c.8157T>A (p.Phe2719Leu) and NM_002111.8(HTT)c.4469+1G>A (Note there are incorrect Clinvar entries). Functional studies show them each to be a hypomorphic mutation, resulting in severe deficiency of huntingtin in compound heterozygotes.

Still only 2 cases reported to date (PMID: 27329733/33432339 and 26740508) with biallelic LOF variants in HTT associated with the LOMARS phenotype although this study add further weight with some functional data.
Intellectual disability v3.1056 HTT Eleanor Williams reviewed gene: HTT: Rating: ; Mode of pathogenicity: None; Publications: 33432339; Phenotypes: Lopes-Maciel-Rodan syndrome OMIM:617435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Thoracic aortic aneurysm or dissection v1.112 PKD1 Dmitrijs Rots reviewed gene: PKD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic epilepsy syndromes v2.336 UFSP2 Sarah Leigh Added comment: Comment on phenotypes: No OMIM reference for the pediatric neurodevelopmental anomalies and epilepsy feautres. Monoallelic variants have previously been associated with skeletal dysplasias (PMIDs 28892125;26428751;32755715), but there does not appear to be any phenotypic overlap between these and the phenotype seen for the biallelic rs142500730.
Genetic epilepsy syndromes v2.336 UFSP2 Sarah Leigh Phenotypes for gene: UFSP2 were changed from Poor weight gain; microcephaly; epilepsy; developmental delay; lack of speech; intellectual disability to Poor weight gain; microcephaly; epilepsy; developmental delay; lack of speech; intellectual disability
Thoracic aortic aneurysm or dissection v1.112 PKD2 Dmitrijs Rots reviewed gene: PKD2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary spastic paraplegia - childhood onset v2.30 FAR1 Arina Puzriakova Classified gene: FAR1 as Amber List (moderate evidence)
Hereditary spastic paraplegia - childhood onset v2.30 FAR1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update
Hereditary spastic paraplegia - childhood onset v2.30 FAR1 Arina Puzriakova Gene: far1 has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia - childhood onset v2.29 FAR1 Arina Puzriakova gene: FAR1 was added
gene: FAR1 was added to Hereditary spastic paraplegia - childhood onset. Sources: Literature
Q2_21_rating tags were added to gene: FAR1.
Mode of inheritance for gene: FAR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FAR1 were set to 25439727; 30561787; 33239752
Phenotypes for gene: FAR1 were set to Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154
Review for gene: FAR1 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and has a 'confirmed' disease confidence rating for 'Severe intellectual disability, epilepsy, and cataracts' in Gene2Phenotype.

Both biallelic and monoallelic variants have been linked to disease; both supported by functional data but showing distinct biochemical phenotypes. Spastic quadriparesis or spasticity were reported in 5/5 patients (4 families - 2 with same founder variant) with biallelic variants (PMIDs: 25439727; 30561787) and spastic paraparesis was a feature in 12/12 patients with heterozygous de novo variants (PMID: 33239752). Paediatric onset.
Sources: Literature
Skeletal dysplasia v2.97 UFSP2 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in unrelated cases with skeletal dysplasia (OMIM:142669 & OMIM:617974). Supportive functional studies presented for one of the variants (PMID 26428751).; to: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in unrelated cases with skeletal dysplasia (OMIM:142669 & OMIM:617974), within the UFSP2 C-terminal C78 peptidase domain, which is required for its catalytic activity. Supportive functional studies presented for one of the variants (PMID 26428751) .
Ataxia and cerebellar anomalies - narrow panel v2.153 TGM6 Ivone Leong commented on gene: TGM6
Ataxia and cerebellar anomalies - narrow panel v2.153 TGM6 Ivone Leong Tag Q2_21_rating tag was added to gene: TGM6.
Ataxia and cerebellar anomalies - narrow panel v2.153 TGM6 Ivone Leong Tag Q2_21_expert_review tag was added to gene: TGM6.
Ataxia and cerebellar anomalies - narrow panel v2.153 TGM6 Ivone Leong Phenotypes for gene: TGM6 were changed from Spinocerebellar ataxia 35, 613908 to Spinocerebellar ataxia 35, OMIM:613908
Ataxia and cerebellar anomalies - narrow panel v2.152 TGM6 Ivone Leong Publications for gene: TGM6 were set to 32426513; 30670339
Ataxia and cerebellar anomalies - narrow panel v2.151 TGM6 Ivone Leong Publications for gene: TGM6 were set to
Ataxia and cerebellar anomalies - narrow panel v2.150 TDP2 Ivone Leong Tag Q2_21_rating tag was added to gene: TDP2.
Ataxia and cerebellar anomalies - narrow panel v2.150 TDP2 Ivone Leong Classified gene: TDP2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.150 TDP2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Ataxia and cerebellar anomalies - narrow panel v2.150 TDP2 Ivone Leong Gene: tdp2 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v2.335 UFSP2 Sarah Leigh Tag Q2_21_rating tag was added to gene: UFSP2.
Genetic epilepsy syndromes v2.335 UFSP2 Sarah Leigh Publications for gene: UFSP2 were set to 33473208
Skeletal dysplasia v2.97 UFSP2 Sarah Leigh Publications for gene: UFSP2 were set to 28892125; 26428751; 32755715
Skeletal dysplasia v2.96 UFSP2 Sarah Leigh Added comment: Comment on phenotypes: A biallelic variant rs142500730 has been associated with pediatric neurodevelopmental anomalies and epilepsy (PMID 33473208).
Skeletal dysplasia v2.96 UFSP2 Sarah Leigh Phenotypes for gene: UFSP2 were changed from ?Beukes Hip Dysplasia OMIM:142669; hip dysplasia, Beukes type MONDO:0007726; ?Spondyloepimetaphyseal dysplasia, Di Rocco type OMIM:617974; spondyloepimetaphyseal dysplasia, di rocco type MONDO:0060702 to ?Beukes Hip Dysplasia OMIM:142669; hip dysplasia, Beukes type MONDO:0007726; ?Spondyloepimetaphyseal dysplasia, Di Rocco type OMIM:617974; spondyloepimetaphyseal dysplasia, di rocco type MONDO:0060702
Skeletal dysplasia v2.95 UFSP2 Sarah Leigh Classified gene: UFSP2 as Amber List (moderate evidence)
Skeletal dysplasia v2.95 UFSP2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Skeletal dysplasia v2.95 UFSP2 Sarah Leigh Gene: ufsp2 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.94 UFSP2 Sarah Leigh Tag Q2_21_rating tag was added to gene: UFSP2.
Skeletal dysplasia v2.94 UFSP2 Sarah Leigh reviewed gene: UFSP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cataracts v2.72 FAR1 Arina Puzriakova changed review comment from: Associated with relevant phenotype in OMIM and has a 'confirmed' disease confidence rating for 'Severe intellectual disability, epilepsy, and cataracts' in Gene2Phenotype.

Both biallelic and monoallelic variants have been linked to disease. Congenital/juvenile cataracts are reported in 4/5 patients (4 families - 2 with same founder variant) with biallelic variants (PMIDs: 25439727; 30561787) and in 12/12 patients with heterozygous de novo variants (PMID: 33239752)
Sources: Literature; to: Associated with relevant phenotype in OMIM and has a 'confirmed' disease confidence rating for 'Severe intellectual disability, epilepsy, and cataracts' in Gene2Phenotype.

Both biallelic and monoallelic variants have been linked to disease; both supported by functional data but showing distinct biochemical phenotypes. Congenital/juvenile cataracts are reported in 4/5 patients (4 families - 2 with same founder variant) with biallelic variants (PMIDs: 25439727; 30561787) and in 12/12 patients with heterozygous de novo variants (PMID: 33239752)
Sources: Literature
Cataracts v2.72 FAR1 Arina Puzriakova Classified gene: FAR1 as Amber List (moderate evidence)
Cataracts v2.72 FAR1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update
Cataracts v2.72 FAR1 Arina Puzriakova Gene: far1 has been classified as Amber List (Moderate Evidence).
Cataracts v2.71 FAR1 Arina Puzriakova gene: FAR1 was added
gene: FAR1 was added to Cataracts. Sources: Literature
Q2_21_rating tags were added to gene: FAR1.
Mode of inheritance for gene: FAR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FAR1 were set to 25439727; 30561787; 33239752
Phenotypes for gene: FAR1 were set to Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154
Review for gene: FAR1 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and has a 'confirmed' disease confidence rating for 'Severe intellectual disability, epilepsy, and cataracts' in Gene2Phenotype.

Both biallelic and monoallelic variants have been linked to disease. Congenital/juvenile cataracts are reported in 4/5 patients (4 families - 2 with same founder variant) with biallelic variants (PMIDs: 25439727; 30561787) and in 12/12 patients with heterozygous de novo variants (PMID: 33239752)
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.149 SPG7 Ivone Leong Tag Q2_21_expert_review tag was added to gene: SPG7.
Ataxia and cerebellar anomalies - narrow panel v2.149 SPG7 Ivone Leong edited their review of gene: SPG7: Added comment: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype.

PMID:33774748. Age of onset reported ranged from 12-61 yo (mean age = 39.1). 25 unrelated families of Irish descent.
PMID:32161564. Age of onset 25 - 45 yo.
PMID:31068484. Age of onset 35.5 +/- 14.3 years (mean age = 50.4). 241 patients were part of the study.
PMID:23065789. Age of onset 10 - 45 yo. 137 patients were part of the study.

As the age of onset is quite a wide range this gene will remain Green to ensure edge cases are identified. This gene has been tagged for GMS expert review on whether this gene's rating needs to be changed.; Changed publications: 33774748, 32161564, 31068484, 23065789
Dilated cardiomyopathy - adult and teen v1.24 RHBDF1 Ivone Leong Classified gene: RHBDF1 as Amber List (moderate evidence)
Dilated cardiomyopathy - adult and teen v1.24 RHBDF1 Ivone Leong Gene: rhbdf1 has been classified as Amber List (Moderate Evidence).
Dilated cardiomyopathy - adult and teen v1.23 RHBDF1 Ivone Leong gene: RHBDF1 was added
gene: RHBDF1 was added to Dilated cardiomyopathy - adult and teen. Sources: Literature
watchlist tags were added to gene: RHBDF1.
Mode of inheritance for gene: RHBDF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RHBDF1 were set to 32870709
Review for gene: RHBDF1 was set to AMBER
Added comment: This gene is rated Amber on the Cardiomyopathies - including childhood onset (Version 1.39) panel with the following reviews:

"Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Ivone Leong (Genomics England Curator), 20 Apr 2021"

"Three families reported with homozygous variants in this gene and onset of DCM in infancy/childhood. Two of the families had the same truncating variant, indicative of founder effect, and one family had a homozygous missense variant. Sources: Literature
Zornitza Stark (Australian Genomics), 16 Apr 2021"
Sources: Literature
Intellectual disability v3.1056 FAR1 Arina Puzriakova Publications for gene: FAR1 were set to 25439727
Intellectual disability v3.1055 FAR1 Arina Puzriakova Tag Q2_21_expert_review tag was added to gene: FAR1.
Tag Q2_21_MOI tag was added to gene: FAR1.
Intellectual disability v3.1055 FAR1 Arina Puzriakova reviewed gene: FAR1: Rating: ; Mode of pathogenicity: None; Publications: 25439727, 30561787, 33239752; Phenotypes: ; Mode of inheritance: None
Cardiomyopathies - including childhood onset v1.39 NRAP Ivone Leong Classified gene: NRAP as Amber List (moderate evidence)
Cardiomyopathies - including childhood onset v1.39 NRAP Ivone Leong Gene: nrap has been classified as Amber List (Moderate Evidence).
Cardiomyopathies - including childhood onset v1.38 NRAP Ivone Leong gene: NRAP was added
gene: NRAP was added to Cardiomyopathies - including childhood onset. Sources: Literature
Q2_21_rating tags were added to gene: NRAP.
Mode of inheritance for gene: NRAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRAP were set to 30384889; 33534821; 28611399; https://doi.org/10.1101/2020.10.12.20211474; 32870709
Phenotypes for gene: NRAP were set to Dilated cardiomyopathy, MONDO:0005021 Edit
Review for gene: NRAP was set to GREEN
Added comment: This gene is Green on the Dilated cardiomyopathy - adult and teen (Version 1.22) with the following reviews:

"This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There are >3 unrelated cases of patients with variants in this gene and having DCM. https://doi.org/10.1101/2020.10.12.20211474 also describes a CRISPR knockout zebrafish which had a cardiac phenotype. Therefore, there is enough evidence to support a gene-disease association and this gene is recommended to be promoted Green at the next panel review. Sources: Literature
Ivone Leong (Genomics England Curator), 25 Feb 2021"

"Twenty unrelated families reported with childhood onset DCM. May be more appropriate for the paediatric cardiomyopathy panel."

As affected individuals have childhood onset DCM it was deemed appropriate to add this gene to this panel as well.
Sources: Literature
Skeletal dysplasia v2.94 UFSP2 Sarah Leigh Mode of inheritance for gene: UFSP2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric disorders - additional genes v1.92 ADAMTS19 Ivone Leong Classified gene: ADAMTS19 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.92 ADAMTS19 Ivone Leong Gene: adamts19 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.91 ADAMTS19 Ivone Leong gene: ADAMTS19 was added
gene: ADAMTS19 was added to Paediatric disorders - additional genes. Sources: Literature
Q2_21_rating, Q2_21_phenotype tags were added to gene: ADAMTS19.
Mode of inheritance for gene: ADAMTS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS19 were set to 31844321; 32323311
Phenotypes for gene: ADAMTS19 were set to Non-syndromic heart valve disease; heart valve disease, MONDO:0002869
Review for gene: ADAMTS19 was set to AMBER
Added comment: This gene is not associated with a phenotype in OMIM or Gene2Phenotype. It is a Green gene on the Familial non syndromic congenital heart disease (Version 1.60) panel with the following reviews:

"New 2020 paper reports 3 additional consanguineous families (2 affected sibs in each) with anomalies of the aortic/pulmonary valves, which included thickening of valve leaflets, stenosis and insufficiency. All 3 families had homozygous LoF variants in ADAMTS19, which segregated with disease. No functional studies. Previously reported 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype
Zornitza Stark (Australian Genomics), 1 Jul 2020"

"PMID: 31844321; Wünnemann 2020: 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Literature
Zornitza Stark (Australian Genomics), 1 May 2020"

After consulting the Genomics England Clinical Team it was decided that this gene should be added to this panel as an Amber gene and subject to GMS specialist review panel to consider whether the isolated phenotype is appropriate for inclusion. If appropriate then this gene should be promoted to Green status.
Sources: Literature
Primary immunodeficiency v2.419 PLG Matthew Buckland gene: PLG was added
gene: PLG was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: PLG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLG were set to PMID: 28795768
Phenotypes for gene: PLG were set to Non-C1 Hereditary Angioedema
Penetrance for gene: PLG were set to unknown
Review for gene: PLG was set to GREEN
Added comment: Bork et al. identified the exon9 mutation in PLG in four index families with normal-C1 hereditary angioedema and a further 9 families studied, with shared clinical features.
Sufficient information to ascribe causality.
Sources: Literature
Skeletal dysplasia v2.93 UFSP2 Sarah Leigh Phenotypes for gene: UFSP2 were changed from Beukes Hip Dysplasia 142669, Spondyloepimetaphyseal dysplasia, Di Rocco type 617974 to ?Beukes Hip Dysplasia OMIM:142669; hip dysplasia, Beukes type MONDO:0007726; ?Spondyloepimetaphyseal dysplasia, Di Rocco type OMIM:617974; spondyloepimetaphyseal dysplasia, di rocco type MONDO:0060702
Skeletal dysplasia v2.92 UFSP2 Sarah Leigh Publications for gene: UFSP2 were set to 28892125; 26428751
Laterality disorders and isomerism v1.45 BRWD1 Ivone Leong Classified gene: BRWD1 as Red List (low evidence)
Laterality disorders and isomerism v1.45 BRWD1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. As only 1 case has situs inversus this gene has been added to this panel as a Red gene.

After discussion with the Genomics England Clinical Team it was decided that this gene would be better suited for the Respiratory ciliopathies including non-CF bronchiectasis (Version 1.45). This gene has been added as an Amber gene with a recommendation for Green status on that panel.
Laterality disorders and isomerism v1.45 BRWD1 Ivone Leong Gene: brwd1 has been classified as Red List (Low Evidence).
Respiratory ciliopathies including non-CF bronchiectasis v1.45 BRWD1 Ivone Leong Classified gene: BRWD1 as Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v1.45 BRWD1 Ivone Leong Gene: brwd1 has been classified as Amber List (Moderate Evidence).
Respiratory ciliopathies including non-CF bronchiectasis v1.44 BRWD1 Ivone Leong gene: BRWD1 was added
gene: BRWD1 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: Literature
Q2_21_rating tags were added to gene: BRWD1.
Mode of inheritance for gene: BRWD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRWD1 were set to 33389130
Phenotypes for gene: BRWD1 were set to Primary ciliary dyskinesia, asthenoteratozoospermia
Review for gene: BRWD1 was set to GREEN
Added comment: This gene is not associated with a phenotype in OMIM or Gene2Phenotype. This gene was added to the Laterality disorders and isomerism (Version 1.44) panel by Zornitza Stark with the following review:

"Biallelic missense variants reported in 3 unrelated individuals. Apart from asthenoteratozoospermia, all 3 had PCD or "PCD-like" symptoms of reccurring airway infections, bronchiectasis, and rhinosinusitis. One individual had situs inversus. Studies on cells from one indivdidual showed abnormal respiratory cilia structure. BRWD1 staining was absent from respiratory cilia in this individual (present in controls). Sources: Literature
Zornitza Stark (Australian Genomics), 7 Feb 2021"

After discussion with the Genomics England Clinical Team it was decided that this gene was better suited to this panel.
Sources: Literature
Laterality disorders and isomerism v1.44 NODAL Ivone Leong commented on gene: NODAL
Laterality disorders and isomerism v1.44 NODAL Ivone Leong Tag Q2_21_expert_review tag was added to gene: NODAL.
Laterality disorders and isomerism v1.44 NKX2-5 Ivone Leong Publications for gene: NKX2-5 were set to 25742962; 26805889
Laterality disorders and isomerism v1.43 NKX2-5 Ivone Leong edited their review of gene: NKX2-5: Added comment: This gene is associated with a phenotype in OMIM and Gene2Phenotype.

PMID: 12414819 describes 2 unrelated families. Family 1: 4 family members with variant in NKX2-5 had atrial septum defect. One of these family members was also diagnosed with polyspenia, midline symmetrical liver, ascending colon and caecum were shifted to the midline and forwards with the small intestine on the left. Family 2: 3 affected family members had atrial septum defect.

PMID: 25118008 describes a proband with a frameshift variant in NKX2-5 with the following phenotypes: double outlet right ventricle, common AV canal, total anomalous pulmonary venous connection, asplenia, failure to thrive and short stature. The proband also had distorted organ position and liver was centrally located and spleen was not identied at 1 week of age. Also had intestinal malformation and underwent Ladd procedure and gastrostomy tube placement at 3 weeks. The authors in this paper notes that NKX2-5 variants are associated with cardiac malformations that are commonly seen in patients with heterotaxy (i.e. transposition of great artieries and double outlet right ventricle) and also with asplenia in some patients.

After discussion with the Genomics England Clinical Team it was decided that this gene should remain Amber on this panel.; Changed rating: AMBER; Changed publications: 12414819, 25118008
Cholestasis v1.83 AP1S1 Ivone Leong Classified gene: AP1S1 as Amber List (moderate evidence)
Cholestasis v1.83 AP1S1 Ivone Leong Gene: ap1s1 has been classified as Amber List (Moderate Evidence).
Cholestasis v1.82 AP1S1 Ivone Leong gene: AP1S1 was added
gene: AP1S1 was added to Cholestasis. Sources: Literature
Q2_21_rating tags were added to gene: AP1S1.
Mode of inheritance for gene: AP1S1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1S1 were set to 32306098; 15668823; 19057675; 23423674; 30244301
Phenotypes for gene: AP1S1 were set to Non-syndromic congenital intestinal failure; MEDNIK syndrome, OMIM:609313
Review for gene: AP1S1 was set to GREEN
Added comment: This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. This gene is also Amber with a recommendation to promote to Green on the Intestinal failure panel (Version 1.40) with the following reviews:

" Established gene-disease association with MEDNIK syndrome - PMID: 32306098 propose a clinical and genetic expansion for AP1S1-associated disease - 2 consanguineous families, each carrying a homozygous missense AP1S1 variant - AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense variants. Sources: Literature
Zornitza Stark (Australian Genomics), 5 Oct 2020"

"This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. After discussion with the Genomics England Clinical Team it was decided that it was appropriate to consider all evidence (including the cases that have an intestinal phenotype for this gene - MEDNIK syndrome), therefore, there is enough evidence to support a gene-disease association. This gene should be rated Green at the next review."

After discussion with the Genomics England Clinical Team it was decided that this gene should also be included in this panel.
Sources: Literature
Hearing loss v2.162 AP1S1 Ivone Leong Classified gene: AP1S1 as Amber List (moderate evidence)
Hearing loss v2.162 AP1S1 Ivone Leong Gene: ap1s1 has been classified as Amber List (Moderate Evidence).
Hearing loss v2.161 AP1S1 Ivone Leong gene: AP1S1 was added
gene: AP1S1 was added to Hearing loss. Sources: Literature
Q2_21_rating tags were added to gene: AP1S1.
Mode of inheritance for gene: AP1S1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP1S1 were set to 32306098; 15668823; 19057675; 23423674; 30244301
Phenotypes for gene: AP1S1 were set to Non-syndromic congenital intestinal failure; MEDNIK syndrome, OMIM:609313
Review for gene: AP1S1 was set to GREEN
Added comment: This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. This gene is also Amber with a recommendation to promote to Green on the Intestinal failure panel (Version 1.40) with the following reviews:

" Established gene-disease association with MEDNIK syndrome - PMID: 32306098 propose a clinical and genetic expansion for AP1S1-associated disease - 2 consanguineous families, each carrying a homozygous missense AP1S1 variant - AP1S1 knockout cell line demonstrated tight-junction and polarity abnormalities that were rescued by WT AP1S1, but not the AP1S1 missense variants. Sources: Literature
Zornitza Stark (Australian Genomics), 5 Oct 2020"

"This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. After discussion with the Genomics England Clinical Team it was decided that it was appropriate to consider all evidence (including the cases that have an intestinal phenotype for this gene - MEDNIK syndrome), therefore, there is enough evidence to support a gene-disease association. This gene should be rated Green at the next review."

After discussion with the Genomics England Clinical Team it was decided that this gene should also be included in this panel.
Sources: Literature
Intellectual disability v3.1055 HERC2 Arina Puzriakova Publications for gene: HERC2 were set to 23065719
Intestinal failure v1.40 AP1S1 Ivone Leong Publications for gene: AP1S1 were set to 32306098; 15668823, 19057675, 23423674, 30244301
Intellectual disability v3.1054 HERC2 Arina Puzriakova Phenotypes for gene: HERC2 were changed from Mental retardation, autosomal recessive 38 to Mental retardation, autosomal recessive 38, OMIM:615516
Intestinal failure v1.39 AP1S1 Ivone Leong Classified gene: AP1S1 as Amber List (moderate evidence)
Intestinal failure v1.39 AP1S1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not in Gene2Phenotype.

After discussion with the Genomics England Clinical Team it was decided that it was appropriate to consider all evidence (including the cases that have an intestinal phenotype for this gene - MEDNIK syndrome), therefore, there is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Intestinal failure v1.39 AP1S1 Ivone Leong Gene: ap1s1 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v2.334 HERC2 Arina Puzriakova Phenotypes for gene: HERC2 were changed from Mental retardation, autosomal recessive 38 (MIM 615516) to Mental retardation, autosomal recessive 38, OMIM:615516
Intestinal failure v1.38 AP1S1 Ivone Leong Tag Q2_21_rating tag was added to gene: AP1S1.
Intestinal failure v1.38 AP1S1 Ivone Leong Phenotypes for gene: AP1S1 were changed from Non-syndromic congenital intestinal failure to Non-syndromic congenital intestinal failure; MEDNIK syndrome, OMIM:609313
Intestinal failure v1.37 AP1S1 Ivone Leong Publications for gene: AP1S1 were set to 32306098
VACTERL-like phenotypes v1.31 PLVAP Ivone Leong Classified gene: PLVAP as Green List (high evidence)
VACTERL-like phenotypes v1.31 PLVAP Ivone Leong Gene: plvap has been classified as Green List (High Evidence).
CAKUT v1.162 PLVAP Ivone Leong Classified gene: PLVAP as Green List (high evidence)
CAKUT v1.162 PLVAP Ivone Leong Gene: plvap has been classified as Green List (High Evidence).
VACTERL-like phenotypes v1.30 PLVAP Ivone Leong gene: PLVAP was added
gene: PLVAP was added to VACTERL-like phenotypes. Sources: Literature
Mode of inheritance for gene: PLVAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLVAP were set to 29875123; 29661969; 26207260; 31215290
Phenotypes for gene: PLVAP were set to Diarrhoea 10, protein-losing enteropathy type, OMIM:618183
Review for gene: PLVAP was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. It is currently Amber with a recommendation to promote to Green on the Intestinal failure panel (Version 1.36) with the following reviews:

"Diarrhoea-10 is a protein-losing enteropathy characterized by intractable secretory diarrhoea and massive protein loss due to leaky fenestrated capillaries. Features include early-onset anasarca, severe hypoalbuminemia, hypogammaglobulinemia, and hypertriglyceridemia, as well as electrolyte abnormalities. Some patients exhibit facial dysmorphism and cardiac and renal anomalies. Intrafamilial variability has been observed, and the disease can be severe, with death occurring in infancy in some patients. Four unrelated families reported. Sources: Expert Review
Zornitza Stark (Australian Genomics), 5 Jan 2021"

"Comment on publications: PMID: 26207260. Patient is of Afgan descent born to consanguineous parents. Presented at 8 days of life with secretory diarrhea, metabolic acidosis, lethargy, poor feeding, and severe hyponatremia causing seizures. Further examination shows patient had bilateral colobomas, undescended testes, mildly dysplastic kidneys bilaterally, low-set ears, and micrognathia. PMID: 29875123. 2 patients (first cousins) from a Muslim Arab consanguineous kindred presented with anasarca, severe hypoalbuminaemia and hypogammaglobinaemia. PMID: 29661969. Patient is of Turkish descent born to consanguineous parents. Presented with severe haematochezia and moderate anasarca. Other findings: dysmorphism, metabolic acidosis, electrolyte deficiencies, elevated GGT, choroid plexus cysts, iris cysts, ASD, VSD, dilated megaureter with dilated renal pelvis, venous thrombosis. PMID: 31215290. Patient born to consanguineous parents. As well as intestinal phenotypes, she also had dysmorphic features, renal and cardiac phenotypes.
Ivone Leong (Genomics England Curator), 12 Apr 2021"

After discussion with the Geomics England Clinical Team it was decided that this gene should also be on this panel.
Sources: Literature
CAKUT v1.161 PLVAP Ivone Leong gene: PLVAP was added
gene: PLVAP was added to CAKUT. Sources: Literature
Mode of inheritance for gene: PLVAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLVAP were set to 29875123; 29661969; 26207260; 31215290
Phenotypes for gene: PLVAP were set to Diarrhoea 10, protein-losing enteropathy type, OMIM:618183
Review for gene: PLVAP was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. It is currently Amber with a recommendation to promote to Green on the Intestinal failure panel (Version 1.36) with the following reviews:

"Diarrhoea-10 is a protein-losing enteropathy characterized by intractable secretory diarrhoea and massive protein loss due to leaky fenestrated capillaries. Features include early-onset anasarca, severe hypoalbuminemia, hypogammaglobulinemia, and hypertriglyceridemia, as well as electrolyte abnormalities. Some patients exhibit facial dysmorphism and cardiac and renal anomalies. Intrafamilial variability has been observed, and the disease can be severe, with death occurring in infancy in some patients. Four unrelated families reported. Sources: Expert Review
Zornitza Stark (Australian Genomics), 5 Jan 2021"

"Comment on publications: PMID: 26207260. Patient is of Afgan descent born to consanguineous parents. Presented at 8 days of life with secretory diarrhea, metabolic acidosis, lethargy, poor feeding, and severe hyponatremia causing seizures. Further examination shows patient had bilateral colobomas, undescended testes, mildly dysplastic kidneys bilaterally, low-set ears, and micrognathia. PMID: 29875123. 2 patients (first cousins) from a Muslim Arab consanguineous kindred presented with anasarca, severe hypoalbuminaemia and hypogammaglobinaemia. PMID: 29661969. Patient is of Turkish descent born to consanguineous parents. Presented with severe haematochezia and moderate anasarca. Other findings: dysmorphism, metabolic acidosis, electrolyte deficiencies, elevated GGT, choroid plexus cysts, iris cysts, ASD, VSD, dilated megaureter with dilated renal pelvis, venous thrombosis. PMID: 31215290. Patient born to consanguineous parents. As well as intestinal phenotypes, she also had dysmorphic features, renal and cardiac phenotypes.
Ivone Leong (Genomics England Curator), 12 Apr 2021"

After discussion with the Geomics England Clinical Team it was decided that this gene should also be on this panel.
Sources: Literature
Intellectual disability v3.1053 NUBPL Arina Puzriakova Phenotypes for gene: NUBPL were changed from MITOCHONDRIAL COMPLEX I DEFICIENCY to Mitochondrial complex I deficiency, nuclear type 21, OMIM:618242
Paediatric disorders - additional genes v1.90 PLVAP Ivone Leong Classified gene: PLVAP as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.90 PLVAP Ivone Leong Gene: plvap has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.89 PLVAP Ivone Leong gene: PLVAP was added
gene: PLVAP was added to Paediatric disorders - additional genes. Sources: Literature
Q2_21_rating tags were added to gene: PLVAP.
Mode of inheritance for gene: PLVAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLVAP were set to 29875123; 29661969; 26207260; 31215290
Phenotypes for gene: PLVAP were set to Diarrhoea 10, protein-losing enteropathy type, OMIM:618183
Review for gene: PLVAP was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. It is currently Amber with a recommendation to promote to Green on the Intestinal failure panel (Version 1.36) with the following reviews:

"Diarrhoea-10 is a protein-losing enteropathy characterized by intractable secretory diarrhoea and massive protein loss due to leaky fenestrated capillaries. Features include early-onset anasarca, severe hypoalbuminemia, hypogammaglobulinemia, and hypertriglyceridemia, as well as electrolyte abnormalities. Some patients exhibit facial dysmorphism and cardiac and renal anomalies. Intrafamilial variability has been observed, and the disease can be severe, with death occurring in infancy in some patients. Four unrelated families reported. Sources: Expert Review
Zornitza Stark (Australian Genomics), 5 Jan 2021"

"Comment on publications: PMID: 26207260. Patient is of Afgan descent born to consanguineous parents. Presented at 8 days of life with secretory diarrhea, metabolic acidosis, lethargy, poor feeding, and severe hyponatremia causing seizures. Further examination shows patient had bilateral colobomas, undescended testes, mildly dysplastic kidneys bilaterally, low-set ears, and micrognathia. PMID: 29875123. 2 patients (first cousins) from a Muslim Arab consanguineous kindred presented with anasarca, severe hypoalbuminaemia and hypogammaglobinaemia. PMID: 29661969. Patient is of Turkish descent born to consanguineous parents. Presented with severe haematochezia and moderate anasarca. Other findings: dysmorphism, metabolic acidosis, electrolyte deficiencies, elevated GGT, choroid plexus cysts, iris cysts, ASD, VSD, dilated megaureter with dilated renal pelvis, venous thrombosis. PMID: 31215290. Patient born to consanguineous parents. As well as intestinal phenotypes, she also had dysmorphic features, renal and cardiac phenotypes.
Ivone Leong (Genomics England Curator), 12 Apr 2021"

After discussion with the Geomics England Clinical Team it was decided that this gene should also be on this panel.
Sources: Literature
Paediatric disorders - additional genes v1.88 FOXP4 Ivone Leong Classified gene: FOXP4 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.88 FOXP4 Ivone Leong Gene: foxp4 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.87 FOXP4 Ivone Leong gene: FOXP4 was added
gene: FOXP4 was added to Paediatric disorders - additional genes. Sources: Literature
Q2_21_phenotype tags were added to gene: FOXP4.
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Review for gene: FOXP4 was set to AMBER
Added comment: This gene is associated with a phenotype in Gene2Phenotype but not in OMIM.

This gene is present as an Amber gene on the Intellectual disability panel (Version 3.1052) with the following reviews:

"This gene is a little bit difficult to place, may be Green on Fetal Anomalies panel? Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays, hence Amber rating here. Sources: Literature
Zornitza Stark (Australian Genomics), 4 Nov 2020"

"Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). As ID is not present in the majority of affected patients, and the affected individuals only show mild ID, this gene has been given an Amber rating.
Ivone Leong (Genomics England Curator), 4 Dec 2020"

After discussion with the Genomics England Clinical Team it was decided that this gene should be added to this panel as an Amber gene and subject to review by the GMS specialist group.
Sources: Literature
Growth failure in early childhood v1.65 FOXP4 Ivone Leong Classified gene: FOXP4 as Amber List (moderate evidence)
Growth failure in early childhood v1.65 FOXP4 Ivone Leong Gene: foxp4 has been classified as Amber List (Moderate Evidence).
Growth failure in early childhood v1.64 FOXP4 Ivone Leong gene: FOXP4 was added
gene: FOXP4 was added to Growth failure in early childhood. Sources: Literature
Q2_21_phenotype tags were added to gene: FOXP4.
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Review for gene: FOXP4 was set to AMBER
Added comment: This gene is associated with a phenotype in Gene2Phenotype but not in OMIM.

This gene is present as an Amber gene on the Intellectual disability panel (Version 3.1052) with the following reviews:

"This gene is a little bit difficult to place, may be Green on Fetal Anomalies panel? Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays, hence Amber rating here. Sources: Literature
Zornitza Stark (Australian Genomics), 4 Nov 2020"

"Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). As ID is not present in the majority of affected patients, and the affected individuals only show mild ID, this gene has been given an Amber rating.
Ivone Leong (Genomics England Curator), 4 Dec 2020"

After discussion with the Genomics England Clinical Team it was decided that this gene should be added to this panel as an Amber gene and subject to review by the GMS specialist group.
Sources: Literature
Fetal anomalies v1.646 FOXP4 Ivone Leong Tag Q2_21_rating was removed from gene: FOXP4.
Fetal anomalies v1.646 FOXP4 Ivone Leong Classified gene: FOXP4 as Amber List (moderate evidence)
Fetal anomalies v1.646 FOXP4 Ivone Leong Gene: foxp4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.645 FOXP4 Ivone Leong gene: FOXP4 was added
gene: FOXP4 was added to Fetal anomalies. Sources: Literature
Q2_21_rating, Q2_21_phenotype tags were added to gene: FOXP4.
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Review for gene: FOXP4 was set to AMBER
Added comment: This gene is associated with a phenotype in Gene2Phenotype but not in OMIM.

This gene is present as an Amber gene on the Intellectual disability panel (Version 3.1052) with the following reviews:

"This gene is a little bit difficult to place, may be Green on Fetal Anomalies panel? Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays, hence Amber rating here. Sources: Literature
Zornitza Stark (Australian Genomics), 4 Nov 2020"

"Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). As ID is not present in the majority of affected patients, and the affected individuals only show mild ID, this gene has been given an Amber rating.
Ivone Leong (Genomics England Curator), 4 Dec 2020"

After discussion with the Genomics England Clinical Team it was decided that this gene should be added to this panel as an Amber gene and subject to review by the GMS specialist group.
Sources: Literature
Hereditary spastic paraplegia - childhood onset v2.28 HPDL Cristina Dias reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32707086, 33188300; Phenotypes: microcephaly, spastic paraplegia, seizures, demyelinating neuropathy, regression, developmental delay, chronic progression, movement disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1052 INPP4A Arina Puzriakova Phenotypes for gene: INPP4A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Intellectual disability; Seizures
Intellectual disability v3.1051 INPP4A Arina Puzriakova Publications for gene: INPP4A were set to 21937992
Intellectual disability v3.1050 INPP4A Arina Puzriakova Classified gene: INPP4A as Amber List (moderate evidence)
Intellectual disability v3.1050 INPP4A Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber. 2 unrelated families with severe ID and biallelic variants in this gene reported to date (PMIDs: 25338135; 31978615)
Intellectual disability v3.1050 INPP4A Arina Puzriakova Gene: inpp4a has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1049 UBE4A Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Zornitza Stark. Sufficient evidence to rate this gene Green at the next GMS panel update - 4 unrelated families with different homozygous LoF variants in UBE4A, supported by some functional data and animal model. Severe ID and GDD was a feature in all affected individuals (8 total).

UBE4A is not associated with any phenotype in OMIM (last edited on 17/09/2010) but has a 'probable' disease confidence rating for 'UBE4A-associated neurodevelopmental disorder' in Gene2Phenotype.; to: Comment on list classification: New gene added by Zornitza Stark. Sufficient evidence to rate this gene Green at the next GMS panel update - PMID:33420346 report 4 unrelated families with different homozygous LoF variants in UBE4A, supported by some functional data and animal model. Severe ID and GDD was a feature in all affected individuals (8 total).

UBE4A is not associated with any phenotype in OMIM (last edited on 17/09/2010) but has a 'probable' disease confidence rating for 'UBE4A-associated neurodevelopmental disorder' in Gene2Phenotype.
Intellectual disability v3.1049 UBE4A Arina Puzriakova Tag Q2_21_rating tag was added to gene: UBE4A.
Intellectual disability v3.1049 UBE4A Arina Puzriakova Classified gene: UBE4A as Amber List (moderate evidence)
Intellectual disability v3.1049 UBE4A Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Sufficient evidence to rate this gene Green at the next GMS panel update - 4 unrelated families with different homozygous LoF variants in UBE4A, supported by some functional data and animal model. Severe ID and GDD was a feature in all affected individuals (8 total).

UBE4A is not associated with any phenotype in OMIM (last edited on 17/09/2010) but has a 'probable' disease confidence rating for 'UBE4A-associated neurodevelopmental disorder' in Gene2Phenotype.
Intellectual disability v3.1049 UBE4A Arina Puzriakova Gene: ube4a has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v2.333 NCDN Arina Puzriakova changed review comment from: Comment on mode of inheritance: Setting MOI to 'Monoallelic' as only one biallelic case reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline.; to: Comment on mode of inheritance: Setting MOI to 'Monoallelic' as only one biallelic case reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline if this gene is upgraded to Green on this panel in the future.
Genetic epilepsy syndromes v2.333 NCDN Arina Puzriakova Classified gene: NCDN as Amber List (moderate evidence)
Genetic epilepsy syndromes v2.333 NCDN Arina Puzriakova Added comment: Comment on list classification: Rating Amber with monoallelic MOI, awaiting further cases with seizures (2/3 de novo cases with epilepsy - PMID: 33711248). Currently 'Red' evidence level for biallelic form.
Genetic epilepsy syndromes v2.333 NCDN Arina Puzriakova Gene: ncdn has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v2.332 NCDN Arina Puzriakova Added comment: Comment on mode of inheritance: Setting MOI to 'Monoallelic' as only one biallelic case reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline.
Genetic epilepsy syndromes v2.332 NCDN Arina Puzriakova Mode of inheritance for gene: NCDN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v2.331 NCDN Arina Puzriakova gene: NCDN was added
gene: NCDN was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: NCDN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NCDN were set to 33711248
Phenotypes for gene: NCDN were set to Intellectual disability; epilepsy
Review for gene: NCDN was set to AMBER
Added comment: NCDN is not yet associated with any phenotype in OMIM (last edited on 08/08/2012) but in Gene2Phenotype monoallelic disease has a 'probable' confidence rating while biallelic variants have a 'possible' disease confidence rating.

- PMID: 33711248 (2021) - Six affected individuals (3 sibs with homozygous missense, and 3 unrelated patients with different de novo missense variants) with variable degrees of DD, ID, and seizures. All 3 sibs had generalised seizures (fever induced in 2), while 2/3 individuals with heterozygous variants developed epileptic spasms presenting several times per day prior to treatment. Supportive functional data included.
Sources: Literature
Intellectual disability v3.1048 NCDN Arina Puzriakova Tag Q2_21_rating tag was added to gene: NCDN.
Intellectual disability v3.1048 NCDN Arina Puzriakova Classified gene: NCDN as Amber List (moderate evidence)
Intellectual disability v3.1048 NCDN Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Sufficient evidence to rate this gene as Green with 'monoallelic' MOI at next GMS panel update.

- PMID: 33711248 (2021) - Six affected individuals (3 sibs with homozygous missense, and 3 unrelated patients with different de novo missense variants) with variable degrees of DD, ID, and seizures. Severity of ID in individuals with heterozygous variants is severe, moderate, and mild (but also learning disabilities), respectively. ID in the 3 sibs was determined as mild. Supportive functional data included.

NCDN is not yet associated with any phenotype in OMIM (last edited on 08/08/2012) but in Gene2Phenotype monoallelic disease has a 'probable' confidence rating while biallelic variants have a 'possible' disease confidence rating.
Intellectual disability v3.1048 NCDN Arina Puzriakova Gene: ncdn has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1047 NCDN Arina Puzriakova Added comment: Comment on mode of inheritance: Setting MOI to 'Monoallelic' as only one biallelic case reported to date, and patients with biallelic variants would still be picked up by the Genomics England pipeline.
Intellectual disability v3.1047 NCDN Arina Puzriakova Mode of inheritance for gene: NCDN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v2.41 MAPKAPK5 Arina Puzriakova Classified gene: MAPKAPK5 as Amber List (moderate evidence)
Limb disorders v2.41 MAPKAPK5 Arina Puzriakova Gene: mapkapk5 has been classified as Amber List (Moderate Evidence).
Limb disorders v2.40 MAPKAPK5 Arina Puzriakova gene: MAPKAPK5 was added
gene: MAPKAPK5 was added to Limb disorders. Sources: Literature
Mode of inheritance for gene: MAPKAPK5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAPKAPK5 were set to 33442026
Phenotypes for gene: MAPKAPK5 were set to Developmental delay, variable brain anomalies, congenital heart defects, dysmorphism; Synpolydactyly
Review for gene: MAPKAPK5 was set to AMBER
Added comment: MAPKAPK5 is not yet associated with any phenotype in OMIM (last edited on 06/04/2016) but has a 'probable' disease confidence rating for 'MAPKAPK5-associated syndrome with synpolydactyly' in Gene2Phenotype.

- PMID: 33442026 (2021) - 3 individuals from 2 families with severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with an additional hypoplastic digit between the fourth and fifth digits of hands and/or feet. Exome sequencing identified different homozygous truncating variants in MAPKAPK5 in both families, segregating with disease and unaffected parents as carriers.

Patient-derived cells showed no expression of MAPKAPK5 protein isoforms and reduced levels of the MAPKAPK5-interacting protein ERK3. F-actin recovery after latrunculin B treatment was found to be less efficient in patient-derived fibroblasts than in control cells, supporting a role of MAPKAPK5 in F-actin polymerization.

Rating Amber, awaiting further cases.
Sources: Literature
Intellectual disability v3.1046 MAPKAPK5 Arina Puzriakova Tag watchlist tag was added to gene: MAPKAPK5.
Intellectual disability v3.1046 MAPKAPK5 Arina Puzriakova Publications for gene: MAPKAPK5 were set to 3344202
Intellectual disability v3.1045 MAPKAPK5 Arina Puzriakova Classified gene: MAPKAPK5 as Amber List (moderate evidence)
Intellectual disability v3.1045 MAPKAPK5 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Rating Amber, awaiting further cases (added watchlist tag)

- PMID: 33442026 report on 2 unrelated families with a comparable phenotype including severe GDD, who harbour different homozygous truncating variants in MAPKAPK5. Some functional evidence indicating the variants impact expression and function of MAPKAPK5 protein.

MAPKAPK5 is not yet associated with any phenotype in OMIM (last edited on 06/04/2016) but has a 'probable' disease confidence rating for 'MAPKAPK5-associated syndrome with synpolydactyly' in Gene2Phenotype.
Intellectual disability v3.1045 MAPKAPK5 Arina Puzriakova Gene: mapkapk5 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.113 COPB1 Arina Puzriakova Classified gene: COPB1 as Amber List (moderate evidence)
Severe microcephaly v2.113 COPB1 Arina Puzriakova Gene: copb1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.112 COPB1 Arina Puzriakova gene: COPB1 was added
gene: COPB1 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: COPB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COPB1 were set to 33632302
Phenotypes for gene: COPB1 were set to Baralle-Macken syndrome, OMIM:619255; Severe intellectual disability; Cataracts; Variable microcephaly
Added comment: COPB1 is associated with a relevant phenotype in OMIM (MIM# 619255) and has a 'possible' disease confidence rating for 'COPB1-related severe intellectual disability syndrome with cataracts and variable microcephaly' in Gene2Phenotype.

- PMID: 33632302 (2021) - six individuals from two unrelated families with different homozygous variants in this gene. Affected patients developed cataracts, severe ID and variable microcephaly - at least 1 individual from each family with microcephaly of relevant severity to this panel (HC ≥ -3SD). Some supportive functional data.

Rating Amber, awaiting further cases.
Sources: Literature
Cataracts v2.70 COPB1 Arina Puzriakova Classified gene: COPB1 as Amber List (moderate evidence)
Cataracts v2.70 COPB1 Arina Puzriakova Gene: copb1 has been classified as Amber List (Moderate Evidence).
Cataracts v2.69 COPB1 Arina Puzriakova gene: COPB1 was added
gene: COPB1 was added to Cataracts. Sources: Literature
Mode of inheritance for gene: COPB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COPB1 were set to 33632302
Phenotypes for gene: COPB1 were set to Baralle-Macken syndrome, OMIM:619255; Severe intellectual disability; Cataracts; Variable microcephaly
Review for gene: COPB1 was set to AMBER
Added comment: COPB1 is associated with a relevant phenotype in OMIM (MIM# 619255) and has a 'possible' disease confidence rating for 'COPB1-related severe intellectual disability syndrome with cataracts and variable microcephaly' in Gene2Phenotype.

- PMID: 33632302 (2021) - six individuals from two unrelated families with different homozygous variants in this gene. All affected patients developed cataracts, among other features such as severe ID and variable microcephaly. Some supportive functional data.

Rating Amber, awaiting further cases.
Sources: Literature
Childhood onset dystonia or chorea or related movement disorder v1.92 SCN1A Dmitrijs Rots reviewed gene: SCN1A: 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: 28794249; Phenotypes: seizures, developmental delay, dystonia, choreoathetosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.1044 COPB1 Arina Puzriakova Tag watchlist tag was added to gene: COPB1.
Intellectual disability v3.1044 COPB1 Arina Puzriakova Classified gene: COPB1 as Amber List (moderate evidence)
Intellectual disability v3.1044 COPB1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. PMID:33632302 reports on six individuals from two unrelated families with different homozygous variants in this gene. All affected patients had severe ID. Rating Amber, awaiting further cases.
Intellectual disability v3.1044 COPB1 Arina Puzriakova Gene: copb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1043 COPB1 Arina Puzriakova Phenotypes for gene: COPB1 were changed from Baralle-Macken syndrome, MIM# 619255; Severe intellectual disability; variable microcephaly; cataracts to Baralle-Macken syndrome, OMIM:619255; Severe intellectual disability; Cataracts; Variable microcephaly
Childhood onset dystonia or chorea or related movement disorder v1.92 ALDH18A1 Sarah Leigh Phenotypes for gene: ALDH18A1 were changed from Cutis laxa, autosomal dominant 3 616603; Cutis laxa, autosomal recessive, type IIIA 219150; Spastic paraplegia 9A, autosomal dominant 601162; Spastic paraplegia 9B, autosomal recessive 616586 to Cutis laxa, autosomal dominant 3 OMIM:616603; cutis laxa, autosomal dominant 3 MONDO:0014706; Cutis laxa, autosomal recessive, type IIIA OMIM:219150; ALDH18A1-related de Barsy syndromeMONDO:0009053; Spastic paraplegia 9A, autosomal dominant OMIM:601162; hereditary spastic paraplegia 9A MONDO:0011006; Spastic paraplegia 9B, autosomal recessive OMIM:616586; autosomal recessive complex spastic paraplegia type 9B MONDO:0014702
Childhood onset dystonia or chorea or related movement disorder v1.91 ALDH18A1 Sarah Leigh Tag Q2_21_phenotype tag was added to gene: ALDH18A1.
Cerebral vascular malformations v2.50 ANGPTL6 Sarah Leigh edited their review of gene: ANGPTL6: Added comment: Not associated with relevant phenotype in OMIM or Gen2Phen. At least 9 variants reported in at least 11 families with Familial Intracranial Aneurysm. Expression and secretion studies have been performed for NM_031917.2. c.1378A>T, p.Lys460Ter, showing that although it is expressed it is not secreted.; Changed rating: GREEN
Cerebral vascular malformations v2.50 ANGPTL6 Sarah Leigh Tag Q2_21_rating tag was added to gene: ANGPTL6.
Cerebral vascular malformations v2.50 ANGPTL6 Sarah Leigh Publications for gene: ANGPTL6 were set to 29304371; 33106390
Cerebral vascular malformations v2.49 ANGPTL6 Sarah Leigh Classified gene: ANGPTL6 as Amber List (moderate evidence)
Cerebral vascular malformations v2.49 ANGPTL6 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Cerebral vascular malformations v2.49 ANGPTL6 Sarah Leigh Gene: angptl6 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v2.48 ANGPTL6 Sarah Leigh Phenotypes for gene: ANGPTL6 were changed from Cerebral aneurysm to brain aneurysm MONDO:0005291
Cystic kidney disease v2.26 FLCN Eleanor Williams Classified gene: FLCN as Amber List (moderate evidence)
Cystic kidney disease v2.26 FLCN Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber, with a recommendation for green rating at the next GMS review.
Cystic kidney disease v2.26 FLCN Eleanor Williams Gene: flcn has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v2.25 FLCN Eleanor Williams Tag Q2_21_rating tag was added to gene: FLCN.
Cystic kidney disease v2.25 FLCN Eleanor Williams commented on gene: FLCN
Cystic kidney disease v2.25 FLCN Eleanor Williams Publications for gene: FLCN were set to PMID: 19785621; 31266032
Cystic kidney disease v2.24 FLCN Eleanor Williams Phenotypes for gene: FLCN were changed from renal cysts; cutaneous fibrofolliculoma; pneumothorax; pulmonary cysts; renal cell carcinoma; renal oncocytoma to Birt-Hogg-Dube syndrome, OMIM:135150; renal cysts; cutaneous fibrofolliculoma; pneumothorax; pulmonary cysts; renal cell carcinoma; renal oncocytoma
White matter disorders and cerebral calcification - narrow panel v1.58 FIG4 Eleanor Williams Classified gene: FIG4 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.58 FIG4 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber, but with a recommendation for green rating at the next GMS review as there are 4 cases with variants in this gene and a leukoencephalopathy phenotype, plus a supportive mouse model.
White matter disorders and cerebral calcification - narrow panel v1.58 FIG4 Eleanor Williams Gene: fig4 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v1.57 FIG4 Eleanor Williams Phenotypes for gene: FIG4 were changed from Charcot-Marie-Tooth disease, type 4J 611228; Yunis-Varon syndrome 216340; leukoencephalopathy to Charcot-Marie-Tooth disease, type 4J, OMIM:611228; Yunis-Varon syndrome, OMIM:216340; leukoencephalopathy, HP:0002352
White matter disorders and cerebral calcification - narrow panel v1.56 FIG4 Eleanor Williams Tag Q2_21_rating tag was added to gene: FIG4.
White matter disorders and cerebral calcification - narrow panel v1.56 FIG4 Eleanor Williams commented on gene: FIG4
White matter disorders and cerebral calcification - narrow panel v1.56 ERCC1 Eleanor Williams changed review comment from: 4 patients reported with biallelic variants in ERCC1. In two cases there were developmental symptoms from birth. In the third neurodegenerative symptoms became apparent at age 15. And in the 4th family liver dysfunction was reported from a young age. No specific mention of white matter abnormalities.

PMID: 17273966 - Jaspers et al 2007 - report a child (165TOR) with cerebro-oculo-facio-skeletal syndrome showing relatively mild impairment of Nucleotide excision repair (NER) but very severe developmental symptoms and death in early infancy. Compound heterozygous variants in ERCC1 were found (one nonsense and and one missense) each inherited from one parent. NMR showed simplified gyral pattern and cerebellar hypoplasia. NO specific white matter abnormalites are reported.

PMID: 23623389 - Kashiyama et al 2013 - through targeted sequencing of ERCC1 and ERCC4 they report 1 patient with a homozygous missense variant. The child was diagnosed with Cockayne syndrome type II. Brain MRI at birth indicated a possible polymicrogyria; a NMR scan at 4 months of age showed large bilateral subdurals but no major visible malformations; at 9 months an abnormal electroencephalogram was recorded.

Imoto K, Boyle J, Oh K, Khan S, Ueda T, Nadem C, Slor H, Orgal S, Gadoth N, Busch D, Jaspers NG, Tamura D, JJ DiGiovanna, Kraemer KH. Patients with defects in the interacting nucleotide excision repair proteins ERCC1 or XPF show xeroderma pigmentosum with late onset severe neurological degeneration. J Invest Dermatol. 2007;127 Supp. 92 - conference abstract - can't access. Review by Gregg et al 2011 (PMID: 21612988) report that this abstract describes a patient with compound het variants in ERCC1 (nonsense mutation and a splicing mutation). The patient showed progressive neurodegeneration from age 15 resulting in dementia and cortical atrophy.

PMID: 33315086 - Apelt et al 2020 - describe 2 siblings with bi-allelic ERCC1 mutations (a missense and a deletion of exon 4) and a unique phenotype of short stature, photosensitivity, progressive cholestatic liver disease, and renal tubulopathy. Mild intellectual disability is reported. Brain magnetic resonance imaging (MRI) at 10 and 12 years for the respective siblings showed mild cerebral atrophy with moderate cerebellar atrophy, and mild brainstem atrophy in one sibling. ; to: 4 patients reported with biallelic variants in ERCC1. In two cases there were developmental symptoms from birth. In the third neurodegenerative symptoms became apparent at age 15. And in the 4th family liver dysfunction was reported from a young age. No specific mention of white matter abnormalities.

PMID: 17273966 - Jaspers et al 2007 - report a child (165TOR) with cerebro-oculo-facio-skeletal syndrome showing relatively mild impairment of Nucleotide excision repair (NER) but very severe developmental symptoms and death in early infancy. Compound heterozygous variants in ERCC1 were found (one nonsense and and one missense) each inherited from one parent. NMR showed simplified gyral pattern and cerebellar hypoplasia. NO specific white matter abnormalites are reported.

PMID: 23623389 - Kashiyama et al 2013 - through targeted sequencing of ERCC1 and ERCC4 they report 1 patient with a homozygous missense variant. The child (CS20LO) was diagnosed with Cockayne syndrome type II. Brain MRI at birth indicated a possible polymicrogyria; a NMR scan at 4 months of age showed large bilateral subdurals but no major visible malformations; at 9 months an abnormal electroencephalogram was recorded.

Imoto K, Boyle J, Oh K, Khan S, Ueda T, Nadem C, Slor H, Orgal S, Gadoth N, Busch D, Jaspers NG, Tamura D, JJ DiGiovanna, Kraemer KH. Patients with defects in the interacting nucleotide excision repair proteins ERCC1 or XPF show xeroderma pigmentosum with late onset severe neurological degeneration. J Invest Dermatol. 2007;127 Supp. 92 - conference abstract - can't access. Review by Gregg et al 2011 (PMID: 21612988) report that this abstract describes a patient with compound het variants in ERCC1 (nonsense mutation and a splicing mutation). The patient showed progressive neurodegeneration from age 15 resulting in dementia and cortical atrophy.

PMID: 33315086 - Apelt et al 2020 - describe 2 siblings with bi-allelic ERCC1 mutations (a missense and a deletion of exon 4) and a unique phenotype of short stature, photosensitivity, progressive cholestatic liver disease, and renal tubulopathy. Mild intellectual disability is reported. Brain magnetic resonance imaging (MRI) at 10 and 12 years for the respective siblings showed mild cerebral atrophy with moderate cerebellar atrophy, and mild brainstem atrophy in one sibling.
Genomic imprinting v0.104 NLRP2 Sarah Leigh changed review comment from: Comment on list classification: Eamonn Maher has recommented a green rating for this gene on this panel. Maternal bialliec variants may result in epigentic distubance of IC2 in imprinting region at 11p15.5 in trans, resulting in Beckwith-Wiedemann syndrome (PMID 19300480) and early embryonic arest, (causing infertility)(PMID 30877238). These findings are supported by a mouse knock out model (PMID 33090377). At least 9 human NLRP2 variants have been identified in families with the above clinical features.; to: Comment on list classification: Eamonn Maher (Department of Medical Genetics, University of Cambridge) has recommented a green rating for this gene on this panel. Maternal bialliec variants may result in epigentic distubance of IC2 in imprinting region at 11p15.5 in trans, resulting in Beckwith-Wiedemann syndrome (PMID 19300480) and early embryonic arest, (causing infertility)(PMID 30877238). These findings are supported by a mouse knock out model (PMID 33090377). At least 9 human NLRP2 variants have been identified in families with the above clinical features.
Genomic imprinting v0.104 KCNQ1OT1 Sarah Leigh reviewed gene: KCNQ1OT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Genomic imprinting v0.104 KCNQ1OT1 Sarah Leigh Publications for gene: KCNQ1OT1 were set to 23511928; 15372379; 30794780; http://igc.otago.ac.nz/home.html; 22205991
Genomic imprinting v0.103 KCNQ1OT1 Sarah Leigh Phenotypes for gene: KCNQ1OT1 were changed from Phenotype resulting from under expression: Beckwith-Wiedemann Syndrome; Affected tissue: all to Beckwith-Wiedemann syndrome OMIM:130650
Genomic imprinting v0.102 KCNQ1OT1 Sarah Leigh Publications for gene: KCNQ1OT1 were set to 23511928; PMID: 15372379; 30794780; http://igc.otago.ac.nz/home.html; 22205991
White matter disorders and cerebral calcification - narrow panel v1.56 ERCC1 Eleanor Williams Publications for gene: ERCC1 were set to 17273966 - ERCC1 deficiency in a patient with cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure; 23623389 - homozygous missense variant reported in a patient with Cockayne syndrome; 21612988
White matter disorders and cerebral calcification - narrow panel v1.55 ERCC1 Eleanor Williams edited their review of gene: ERCC1: Changed publications: 17273966, 23623389, 21612988, 33315086
White matter disorders and cerebral calcification - narrow panel v1.55 ERCC1 Eleanor Williams changed review comment from: 3 patients reported with biallelic variants in ERCC1. In two cases there were developmental symptoms from birth. In the third neurodegenerative symptoms became apparent at age 15. No specific mention of white matter abnormalities.

PMID: 17273966 - Jaspers et al 2007 - report a child (165TOR) with cerebro-oculo-facio-skeletal syndrome showing relatively mild impairment of Nucleotide excision repair (NER) but very severe developmental symptoms and death in early infancy. Compound heterozygous variants in ERCC1 were found (one nonsense and and one missense) each inherited from one parent. NMR showed simplified gyral pattern and cerebellar hypoplasia. NO specific white matter abnormalites are reported.

PMID: 23623389 - Kashiyama et al 2013 - through targeted sequencing of ERCC1 and ERCC4 they report 1 patient with a homozygous missense variant. The child was diagnosed with Cockayne syndrome type II. Brain MRI at birth indicated a possible polymicrogyria; a NMR scan at 4 months of age showed large bilateral subdurals but no major visible malformations; at 9 months an abnormal electroencephalogram was recorded.

Imoto K, Boyle J, Oh K, Khan S, Ueda T, Nadem C, Slor H, Orgal S, Gadoth N, Busch D, Jaspers NG, Tamura D, JJ DiGiovanna, Kraemer KH. Patients with defects in the interacting nucleotide excision repair proteins ERCC1 or XPF show xeroderma pigmentosum with late onset severe neurological degeneration. J Invest Dermatol. 2007;127 Supp. 92 - can't access paper. Not in PubMed but review by Gregg et al 2011 (PMID: 21612988) report that it describes a patient with compound het variants in ERCC1 (nonsense mutation and a splicing mutation). The patient showed progressive neurodegeneration from age 15 resulting in dementia and cortical atrophy.; to: 4 patients reported with biallelic variants in ERCC1. In two cases there were developmental symptoms from birth. In the third neurodegenerative symptoms became apparent at age 15. And in the 4th family liver dysfunction was reported from a young age. No specific mention of white matter abnormalities.

PMID: 17273966 - Jaspers et al 2007 - report a child (165TOR) with cerebro-oculo-facio-skeletal syndrome showing relatively mild impairment of Nucleotide excision repair (NER) but very severe developmental symptoms and death in early infancy. Compound heterozygous variants in ERCC1 were found (one nonsense and and one missense) each inherited from one parent. NMR showed simplified gyral pattern and cerebellar hypoplasia. NO specific white matter abnormalites are reported.

PMID: 23623389 - Kashiyama et al 2013 - through targeted sequencing of ERCC1 and ERCC4 they report 1 patient with a homozygous missense variant. The child was diagnosed with Cockayne syndrome type II. Brain MRI at birth indicated a possible polymicrogyria; a NMR scan at 4 months of age showed large bilateral subdurals but no major visible malformations; at 9 months an abnormal electroencephalogram was recorded.

Imoto K, Boyle J, Oh K, Khan S, Ueda T, Nadem C, Slor H, Orgal S, Gadoth N, Busch D, Jaspers NG, Tamura D, JJ DiGiovanna, Kraemer KH. Patients with defects in the interacting nucleotide excision repair proteins ERCC1 or XPF show xeroderma pigmentosum with late onset severe neurological degeneration. J Invest Dermatol. 2007;127 Supp. 92 - conference abstract - can't access. Review by Gregg et al 2011 (PMID: 21612988) report that this abstract describes a patient with compound het variants in ERCC1 (nonsense mutation and a splicing mutation). The patient showed progressive neurodegeneration from age 15 resulting in dementia and cortical atrophy.

PMID: 33315086 - Apelt et al 2020 - describe 2 siblings with bi-allelic ERCC1 mutations (a missense and a deletion of exon 4) and a unique phenotype of short stature, photosensitivity, progressive cholestatic liver disease, and renal tubulopathy. Mild intellectual disability is reported. Brain magnetic resonance imaging (MRI) at 10 and 12 years for the respective siblings showed mild cerebral atrophy with moderate cerebellar atrophy, and mild brainstem atrophy in one sibling.
Genomic imprinting v0.101 NLRP2 Sarah Leigh changed review comment from: Comment on list classification: Maternal bialliec variants may result in epigentic distubance of IC2 in imprinting region at 11p15.5 in trans, resulting in Beckwith-Wiedemann syndrome (PMID 19300480) and early embryonic arest, (causing infertility)(PMID 30877238). These findings are supported by a mouse knock out model (PMID 33090377). At least 9 human NLRP2 variants have been identified in families with the above clinical features.; to: Comment on list classification: Eamonn Maher has recommented a green rating for this gene on this panel. Maternal bialliec variants may result in epigentic distubance of IC2 in imprinting region at 11p15.5 in trans, resulting in Beckwith-Wiedemann syndrome (PMID 19300480) and early embryonic arest, (causing infertility)(PMID 30877238). These findings are supported by a mouse knock out model (PMID 33090377). At least 9 human NLRP2 variants have been identified in families with the above clinical features.
Growth failure in early childhood v1.63 NLRP2 Sarah Leigh Publications for gene: NLRP2 were set to 26323243; 29574422; 19300480; 30877238; 33090377
Segmental overgrowth disorders v2.13 NLRP2 Sarah Leigh Classified gene: NLRP2 as Amber List (moderate evidence)
Segmental overgrowth disorders v2.13 NLRP2 Sarah Leigh Gene: nlrp2 has been classified as Amber List (Moderate Evidence).
Segmental overgrowth disorders v2.12 NLRP2 Sarah Leigh Added comment: Comment on mode of pathogenicity: Maternal NLRP2 variants result in epigenitic disturbance at sites in trans, eg: IC2 in imprinting region at 11p15.5 (PMID 19300480).
Segmental overgrowth disorders v2.12 NLRP2 Sarah Leigh Mode of pathogenicity for gene: NLRP2 was changed from Other to Other
Segmental overgrowth disorders v2.11 NLRP2 Sarah Leigh gene: NLRP2 was added
gene: NLRP2 was added to Segmental overgrowth disorders. Sources: Literature
Mode of inheritance for gene: NLRP2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NLRP2 were set to 26323243; 29574422; 19300480; 30877238; 33090377
Phenotypes for gene: NLRP2 were set to Beckwith-Wiedemann syndrome due to imprinting defect of 11p15 MONDO:0016475
Mode of pathogenicity for gene: NLRP2 was set to Other
Review for gene: NLRP2 was set to AMBER
Added comment: Maternal bialliec variants may result in epigentic distubance of IC2 in imprinting region at 11p15.5 in trans, resulting in Beckwith-Wiedemann syndrome (PMID 19300480) and early embryonic arest, (causing infertility)(PMID 30877238). These findings are supported by a mouse knock out model (PMID 33090377). At least 9 human NLRP2 variants have been identified in families with the above clinical features.
Sources: Literature
Genomic imprinting v0.101 NLRP2 Sarah Leigh changed review comment from: Comment on list classification: Maternal bialliec variants may result in: epigentic distubance of IC2 in imprinting region at 11p15.5 in trans, resulting in Beckwith-Wiedemann syndrome (PMID 19300480), early embryonic arest, (causing infertility)(PMID 30877238). These findings are supported by a mouse knock out model (PMID 33090377). At least 9 human NLRP2 variants have been identified in families with the above clinical features.; to: Comment on list classification: Maternal bialliec variants may result in epigentic distubance of IC2 in imprinting region at 11p15.5 in trans, resulting in Beckwith-Wiedemann syndrome (PMID 19300480) and early embryonic arest, (causing infertility)(PMID 30877238). These findings are supported by a mouse knock out model (PMID 33090377). At least 9 human NLRP2 variants have been identified in families with the above clinical features.
Growth failure in early childhood v1.62 NLRP2 Sarah Leigh edited their review of gene: NLRP2: Added comment: Maternal bialliec variants may result in: epigentic distubance of IC2 in imprinting region at 11p15.5 in trans, resulting in Beckwith-Wiedemann syndrome (PMID 19300480), early embryonic arest, (causing infertility)(PMID 30877238). These findings are supported by a mouse knock out model (PMID 33090377). At least 9 human NLRP2 variants have been identified in families with the above clinical features.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genomic imprinting v0.101 NLRP2 Sarah Leigh changed review comment from: Comment on list classification: Bialliec variants in a mother may result in: epigentic distubance of IC2 in imprinting region at 11p15.5 in trans, resulting in Beckwith-Wiedemann syndrome (PMID 19300480), early embryonic arest, (causing infertility)(PMID 30877238). These findings are supported by a mouse knock out model (PMID 33090377). At least 9 human NLRP2 variants have been identified in families with the above clinical features.; to: Comment on list classification: Maternal bialliec variants may result in: epigentic distubance of IC2 in imprinting region at 11p15.5 in trans, resulting in Beckwith-Wiedemann syndrome (PMID 19300480), early embryonic arest, (causing infertility)(PMID 30877238). These findings are supported by a mouse knock out model (PMID 33090377). At least 9 human NLRP2 variants have been identified in families with the above clinical features.
Genomic imprinting v0.101 NLRP2 Sarah Leigh changed review comment from: Comment on mode of pathogenicity: NLRP2 variants result in epigenitic disturbance at sites in trans, eg IC2 in imprinting region at 11p15.5 (PMID 19300480).; to: Comment on mode of pathogenicity: Maternal NLRP2 variants result in epigenitic disturbance at sites in trans, eg: IC2 in imprinting region at 11p15.5 (PMID 19300480).
Genomic imprinting v0.101 NLRP2 Sarah Leigh Phenotypes for gene: NLRP2 were changed from Phenotype resulting from under expression: Beckwith-Wiedemann Syndrome. Multi-locus imprinting disorder; Affected tissue: all to Beckwith-Wiedemann syndrome due to imprinting defect of 11p15 MONDO:0016475
Genomic imprinting v0.100 NLRP2 Sarah Leigh Added comment: Comment on mode of pathogenicity: NLRP2 variants result in epigenitic disturbance at sites in trans, eg IC2 in imprinting region at 11p15.5 (PMID 19300480).
Genomic imprinting v0.100 NLRP2 Sarah Leigh Mode of pathogenicity for gene: NLRP2 was changed from to Other
Genomic imprinting v0.99 NLRP2 Sarah Leigh Classified gene: NLRP2 as Green List (high evidence)
Genomic imprinting v0.99 NLRP2 Sarah Leigh Added comment: Comment on list classification: Bialliec variants in a mother may result in: epigentic distubance of IC2 in imprinting region at 11p15.5 in trans, resulting in Beckwith-Wiedemann syndrome (PMID 19300480), early embryonic arest, (causing infertility)(PMID 30877238). These findings are supported by a mouse knock out model (PMID 33090377). At least 9 human NLRP2 variants have been identified in families with the above clinical features.
Genomic imprinting v0.99 NLRP2 Sarah Leigh Gene: nlrp2 has been classified as Green List (High Evidence).
White matter disorders and cerebral calcification - narrow panel v1.55 ERCC1 Eleanor Williams Classified gene: ERCC1 as Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v1.55 ERCC1 Eleanor Williams Added comment: Comment on list classification: Leaving rating as green for now, but with recommendation for amber or red rating at the next GMS review. There does not appear to be evidence that this is a white matter disorder.
White matter disorders and cerebral calcification - narrow panel v1.55 ERCC1 Eleanor Williams Gene: ercc1 has been classified as Green List (High Evidence).
White matter disorders and cerebral calcification - narrow panel v1.54 ERCC1 Eleanor Williams Publications for gene: ERCC1 were set to 17273966 - ERCC1 deficiency in a patient with cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure; 23623389 - homozygous missense variant reported in a patient with Cockayne syndrome
White matter disorders and cerebral calcification - narrow panel v1.53 ERCC1 Eleanor Williams edited their review of gene: ERCC1: Added comment: 3 patients reported with biallelic variants in ERCC1. In two cases there were developmental symptoms from birth. In the third neurodegenerative symptoms became apparent at age 15. No specific mention of white matter abnormalities.

PMID: 17273966 - Jaspers et al 2007 - report a child (165TOR) with cerebro-oculo-facio-skeletal syndrome showing relatively mild impairment of Nucleotide excision repair (NER) but very severe developmental symptoms and death in early infancy. Compound heterozygous variants in ERCC1 were found (one nonsense and and one missense) each inherited from one parent. NMR showed simplified gyral pattern and cerebellar hypoplasia. NO specific white matter abnormalites are reported.

PMID: 23623389 - Kashiyama et al 2013 - through targeted sequencing of ERCC1 and ERCC4 they report 1 patient with a homozygous missense variant. The child was diagnosed with Cockayne syndrome type II. Brain MRI at birth indicated a possible polymicrogyria; a NMR scan at 4 months of age showed large bilateral subdurals but no major visible malformations; at 9 months an abnormal electroencephalogram was recorded.

Imoto K, Boyle J, Oh K, Khan S, Ueda T, Nadem C, Slor H, Orgal S, Gadoth N, Busch D, Jaspers NG, Tamura D, JJ DiGiovanna, Kraemer KH. Patients with defects in the interacting nucleotide excision repair proteins ERCC1 or XPF show xeroderma pigmentosum with late onset severe neurological degeneration. J Invest Dermatol. 2007;127 Supp. 92 - can't access paper. Not in PubMed but review by Gregg et al 2011 (PMID: 21612988) report that it describes a patient with compound het variants in ERCC1 (nonsense mutation and a splicing mutation). The patient showed progressive neurodegeneration from age 15 resulting in dementia and cortical atrophy.; Changed rating: AMBER; Changed publications: 17273966, 23623389, 21612988; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.53 ERCC1 Eleanor Williams Added comment: Comment on phenotypes: Only associated with Cerebrooculofacioskeletal syndrome 4 in OMIM and Gene2Phenotype so removing Xeroderma pigmentosum as a phenotype.
White matter disorders and cerebral calcification - narrow panel v1.53 ERCC1 Eleanor Williams Phenotypes for gene: ERCC1 were changed from Xeroderma Pigmentosum to Cerebrooculofacioskeletal syndrome 4, OMIM:610758
Genomic imprinting v0.98 NLRP2 Sarah Leigh changed review comment from: Not associated with relevant phenotype in OMIM or in Gen2Phen. As a NLRP gene, NLRP2 has epigenetic control of imprinted regions that are part of Multi Locus Imprinting Disturbances.

Review from imprinting expert: A number of patients with IUGR and failure of catch up have an imprinting error (withiin the spectrum of Silver Russell syndrome, temple syndrome) ithat s caused by mutations in NLRP2 in the MOTHER of the patient. Note that LOF mutations (homozygous or heterozygous mutations) identified in the mother would lead to further patient testing for multilocus imprinting disturbance through methylation testing.
Karen Temple (Wessex GMC), 29 Jan 2021; to: Not associated with relevant phenotype in OMIM or in Gen2Phen. As a NLRP gene, NLRP2 has epigenetic control of imprinted regions that are part of Multi Locus Imprinting Disturbances.

Review from imprinting expert: A number of patients with IUGR and failure of catch up have an imprinting error (withiin the spectrum of Silver Russell syndrome, temple syndrome) that is caused by variants in NLRP2 in the MOTHER of the patient. Note that LOF mutations (homozygous or heterozygous mutations) identified in the mother would lead to further patient testing for multilocus imprinting disturbance through methylation testing.
Karen Temple (Wessex GMC), 29 Jan 2021
Cerebral vascular malformations v2.47 SETD5 Sarah Leigh Classified gene: SETD5 as Red List (low evidence)
Cerebral vascular malformations v2.47 SETD5 Sarah Leigh Added comment: Comment on list classification: Associated with Mental retardation, autosomal dominant 23 OMIM:615761 in OMIM and as confirmed Gen2Phen gene. At least one de novo variant has been reported a case of Moyamoya disease MONDO:0016820, who also had features of OMIM:615761.
Cerebral vascular malformations v2.47 SETD5 Sarah Leigh Gene: setd5 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v2.46 SETD5 Sarah Leigh Phenotypes for gene: SETD5 were changed from MoyaMoya; Mental retardation, autosomal dominant 23 OMIM:615761; intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency MONDO:0014336 to Moyamoya disease MONDO:0016820; Mental retardation, autosomal dominant 23 OMIM:615761; intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency MONDO:0014336
Cerebral vascular malformations v2.45 CHD4 Sarah Leigh Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome OMIM:617159; Sifrim-Hitz-Weiss syndrome MONDO:0014946 to Moyamoya disease MONDO:0016820; Sifrim-Hitz-Weiss syndrome OMIM:617159; Sifrim-Hitz-Weiss syndrome MONDO:0014946
Cerebral vascular malformations v2.44 CHD4 Sarah Leigh changed review comment from: Comment on list classification: PMID 31474762 reports variants in CHD4 cases of Moya Moya, this is a new gene / condition association. Moya Moya is relevant to this panel - Cerebral vascular malformations. So far there is not enough evidence for this gene to be amber or green for Moya Moya.; to: Comment on list classification: PMID 31474762 reports variants in CHD4 cases of Moyamoya disease MONDO:0016820, this is a new gene / condition association. Moyamoya is relevant to this panel - Cerebral vascular malformations. So far there is not enough evidence for this gene to be amber or green for Moyamoya.
Cerebral vascular malformations v2.44 CNOT3 Sarah Leigh Phenotypes for gene: CNOT3 were changed from Intellectual developmental disorder with speech delay, autism, and dysmorphic facies OMIM:618672; intellectual developmental disorder with speech delay, autism, and dysmorphic facies MONDO:0032864 to Moyamoya disease MONDO:0016820; Intellectual developmental disorder with speech delay, autism, and dysmorphic facies OMIM:618672; intellectual developmental disorder with speech delay, autism, and dysmorphic facies MONDO:0032864
Cerebral vascular malformations v2.43 CNOT3 Sarah Leigh changed review comment from: Comment on list classification: Associated with Intellectual developmental disorder with speech delay, autism, and dysmorphic facies (OMIM:618672) in OMIM and as confirmed Gen2Phen gene for CNOT3 syndrome. At least two de novo variants have been reported in two cases with Moyamoya angiopathy (MMA), who also had some of the features of OMIM:618672.; to: Comment on list classification: Associated with Intellectual developmental disorder with speech delay, autism, and dysmorphic facies (OMIM:618672) in OMIM and as confirmed Gen2Phen gene for CNOT3 syndrome. At least two de novo variants have been reported in two cases with Moyamoya disease MONDO:0016820, who also had some of the features of OMIM:618672.
White matter disorders and cerebral calcification - narrow panel v1.52 EPRS Eleanor Williams Classified gene: EPRS as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.52 EPRS Eleanor Williams Gene: eprs has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v1.51 EPRS Eleanor Williams Tag Q2_21_rating tag was added to gene: EPRS.
White matter disorders and cerebral calcification - narrow panel v1.51 EPRS Eleanor Williams Classified gene: EPRS as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.51 EPRS Eleanor Williams Added comment: Comment on list classification: promoting from grey to amber but with recommendation for green rating following GMS review. 4 unrelated cases, presentation before age of 18.
White matter disorders and cerebral calcification - narrow panel v1.51 EPRS Eleanor Williams Gene: eprs has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v2.43 SETD5 Sarah Leigh Phenotypes for gene: SETD5 were changed from Moya Moya; Mental retardation, autosomal dominant 23, MIM# 615761 to MoyaMoya; Mental retardation, autosomal dominant 23 OMIM:615761; intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency MONDO:0014336
Genetic epilepsy syndromes v2.330 UFSP2 Tracy Lester gene: UFSP2 was added
gene: UFSP2 was added to Genetic epilepsy syndromes. Sources: NHS GMS
Mode of inheritance for gene: UFSP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UFSP2 were set to 33473208
Phenotypes for gene: UFSP2 were set to Poor weight gain; microcephaly; epilepsy; developmental delay; lack of speech; intellectual disability
Penetrance for gene: UFSP2 were set to Complete
Mode of pathogenicity for gene: UFSP2 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: UFSP2 was set to GREEN
Added comment: This is a founder variant that has been reported homozygously in several individuals with an epileptic encephalopathy like phenotype. Three additional cases have been identified in the GEL 100K database by the MSK GeCIP. Recessive LOF variants in this gene cause a skeletal dysplasia phenotype. Functional studies support a gain of function for this variant.
Sources: NHS GMS
White matter disorders and cerebral calcification - narrow panel v1.50 EPRS Eleanor Williams edited their review of gene: EPRS: Added comment: As reported by the expert reviewer PMID: 29576217 (Mendes et al 2018) reports 4 unrelated affected individuals with hypomyelination and biallelic (homozygous or compound het) pathogenic variants in EPRS. 5 variants in total identified (1 nonsense, 1 frameshift, 3 missense). Variants segregated with the disease in all 4 families. All 4 presented initially before the age of 18 and in all brain MRI showed a hypomyelinating leukodystrophy with thinning of the corpus callosum. In 3 cases the variant was identified by WES, in one by direct sequencing of EPRS1.

PMID: 33805425 - Sawaguchi et al 2021 - using a mouse model they show that EPRS1 variant Arg339-to-Ter (R339X) (found in one of the patients in Mendes et al in heterozgyous state with another variant) localizes EPRS1 proteins as polymeric aggregates into Rab7-positive vesicle structures in mouse oligodendroglial FBD-102b cells. Wild-type proteins are distributed throughout the cell bodies. This seems to inhibit cell morphological differentiation.; Changed rating: GREEN; Changed publications: 29576217, 33805425; Changed phenotypes: Leukodystrophy, hypomyelinating, 15, OMIM:617951; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v2.42 CNOT3 Sarah Leigh changed review comment from: Comment on list classification: Associated with Intellectual developmental disorder with speech delay, autism, and dysmorphic facies OMIM:618672 in OMIM and as confirmed Gen2Phen gene for CNOT3 syndrome. At least two de novo variants have been reported in two cases with Moyamoya angiopathy (MMA), in addition to some of the features of OMIM:618672.; to: Comment on list classification: Associated with Intellectual developmental disorder with speech delay, autism, and dysmorphic facies (OMIM:618672) in OMIM and as confirmed Gen2Phen gene for CNOT3 syndrome. At least two de novo variants have been reported in two cases with Moyamoya angiopathy (MMA), who also had some of the features of OMIM:618672.
Cerebral vascular malformations v2.42 CNOT3 Sarah Leigh Classified gene: CNOT3 as Amber List (moderate evidence)
Cerebral vascular malformations v2.42 CNOT3 Sarah Leigh Added comment: Comment on list classification: Associated with Intellectual developmental disorder with speech delay, autism, and dysmorphic facies OMIM:618672 in OMIM and as confirmed Gen2Phen gene for CNOT3 syndrome. At least two de novo variants have been reported in two cases with Moyamoya angiopathy (MMA), in addition to some of the features of OMIM:618672.
Cerebral vascular malformations v2.42 CNOT3 Sarah Leigh Gene: cnot3 has been classified as Amber List (Moderate Evidence).
Cerebral vascular malformations v2.41 CNOT3 Sarah Leigh Phenotypes for gene: CNOT3 were changed from Moya Moya; Intellectual developmental disorder with speech delay, autism, and dysmorphic facies, MIM# 618672 to Intellectual developmental disorder with speech delay, autism, and dysmorphic facies OMIM:618672; intellectual developmental disorder with speech delay, autism, and dysmorphic facies MONDO:0032864
White matter disorders - adult onset v1.8 EPRS Eleanor Williams commented on gene: EPRS
White matter disorders - adult onset v1.8 EPRS Eleanor Williams Tag new-gene-name tag was added to gene: EPRS.
White matter disorders and cerebral calcification - narrow panel v1.50 EPRS Eleanor Williams commented on gene: EPRS
White matter disorders and cerebral calcification - narrow panel v1.50 EPRS Eleanor Williams Tag new-gene-name tag was added to gene: EPRS.
Cerebral vascular malformations v2.40 CHD4 Sarah Leigh changed review comment from: Comment on list classification: PMID 31474762 reports variants in CHD4 cases of Moya Moya, this is a new gene condition association. Moya Moya is relevant to this panel -Cerebral vascular malformations. So far there is not enough evidence for this gene to be amber or green for Moya Moya.; to: Comment on list classification: PMID 31474762 reports variants in CHD4 cases of Moya Moya, this is a new gene / condition association. Moya Moya is relevant to this panel - Cerebral vascular malformations. So far there is not enough evidence for this gene to be amber or green for Moya Moya.
Cerebral vascular malformations v2.40 CHD4 Sarah Leigh Classified gene: CHD4 as Red List (low evidence)
Cerebral vascular malformations v2.40 CHD4 Sarah Leigh Added comment: Comment on list classification: PMID 31474762 reports variants in CHD4 cases of Moya Moya, this is a new gene condition association. Moya Moya is relevant to this panel -Cerebral vascular malformations. So far there is not enough evidence for this gene to be amber or green for Moya Moya.
Cerebral vascular malformations v2.40 CHD4 Sarah Leigh Gene: chd4 has been classified as Red List (Low Evidence).
Cerebral vascular malformations v2.39 CHD4 Sarah Leigh Publications for gene: CHD4 were set to 31474762; 27616479
Cerebral vascular malformations v2.38 CHD4 Sarah Leigh Publications for gene: CHD4 were set to 31474762
Fetal anomalies v1.644 CHD4 Sarah Leigh Added comment: Comment on phenotypes: Syndromic INTELLECTUAL DISABILITY with or without congenital heart disease
Fetal anomalies v1.644 CHD4 Sarah Leigh Phenotypes for gene: CHD4 were changed from Syndromic INTELLECTUAL DISABILITY with or without congenital heart disease to Sifrim-Hitz-Weiss syndrome OMIM:617159; Sifrim-Hitz-Weiss syndrome MONDO:0014946
Intellectual disability v3.1042 CHD4 Sarah Leigh Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome 617159 to Sifrim-Hitz-Weiss syndrome OMIM:617159; Sifrim-Hitz-Weiss syndrome MONDO:0014946
Cerebral vascular malformations v2.37 CHD4 Sarah Leigh Phenotypes for gene: CHD4 were changed from Moya Moya; Sifrim-Hitz-Weiss syndrome, MIM# 617159 to Sifrim-Hitz-Weiss syndrome OMIM:617159; Sifrim-Hitz-Weiss syndrome MONDO:0014946
Arthrogryposis v3.98 ERBB3 Sarah Leigh edited their review of gene: ERBB3: Added comment: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene for Lethal congenital contractural syndrome 2 OMIM:607598 and as a confirmed gene for Hirschprung disease with intestinal pseudo-obstruction. At least 7 variants reported in at least 4 unrelated cases.; Changed rating: GREEN
Arthrogryposis v3.98 ERBB3 Sarah Leigh Tag Q2_21_rating tag was added to gene: ERBB3.
Arthrogryposis v3.98 ERBB3 Sarah Leigh Classified gene: ERBB3 as Amber List (moderate evidence)
Arthrogryposis v3.98 ERBB3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Arthrogryposis v3.98 ERBB3 Sarah Leigh Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v3.97 ERBB3 Sarah Leigh Publications for gene: ERBB3 were set to 17701904; 12519750
Arthrogryposis v3.96 ERBB3 Sarah Leigh Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2 607598 to ?Lethal congenital contractural syndrome 2 OMIM:607598; lethal congenital contracture syndrome 2 MONDO:0011868
Skeletal dysplasia v2.91 FBN2 Sarah Leigh Deleted their comment
Skeletal dysplasia v2.91 FBN2 Sarah Leigh commented on gene: FBN2: It would appear from PMIDs 33571691, 25558065 & 28383543 that biallelic variants should be considered for this gene and as such the MOI should be changed to BOTH monallelic and biallelic, autosomal or pseudoautosomal.
DDG2P v2.27 FBN2 Sarah Leigh commented on gene: FBN2: It would appear from PMIDs 33571691, 25558065 & 28383543 that biallelic variants should be considered for this gene and as such the MOI should be changed to BOTH monallelic and biallelic, autosomal or pseudoautosomal.
DDG2P v2.27 FBN2 Sarah Leigh reviewed gene: FBN2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.643 FBN2 Sarah Leigh reviewed gene: FBN2: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.91 FBN2 Sarah Leigh edited their review of gene: FBN2: Added comment: It would appear from PMIDs 33571691, 25558065 & 28383543 that biallelic variants should be considered for this gene and as such the MOI should be changed to BOTH monallelic and biallelic, autosomal or pseudoautosomal.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.91 FBN2 Sarah Leigh Phenotypes for gene: FBN2 were changed from Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363 to Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363
DDG2P v2.27 FBN2 Sarah Leigh Phenotypes for gene: FBN2 were changed from CONGENITAL CONTRACTURAL ARACHNODACTYLY 121050 to Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363
Fetal anomalies v1.643 FBN2 Sarah Leigh Phenotypes for gene: FBN2 were changed from CONGENITAL CONTRACTURAL ARACHNODACTYLY to Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363
Skeletal dysplasia v2.90 FBN2 Sarah Leigh Phenotypes for gene: FBN2 were changed from Contractural arachnodactyly, congenital 121050 to Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363
Skeletal dysplasia v2.89 FBN2 Sarah Leigh Publications for gene: FBN2 were set to 7493032; 33571691; 25558065; 28383543
DDG2P v2.26 FBN2 Sarah Leigh Publications for gene: FBN2 were set to 10797416; 11281275; 9199560; 8900230; 9737771; 20799338; 9106527
DDG2P v2.25 FBN2 Sarah Leigh Tag Q2_21_MOI tag was added to gene: FBN2.
Fetal anomalies v1.642 FBN2 Sarah Leigh Publications for gene: FBN2 were set to
Skeletal dysplasia v2.88 FBN2 Sarah Leigh Publications for gene: FBN2 were set to
Fetal anomalies v1.641 FBN2 Sarah Leigh Tag Q2_21_MOI tag was added to gene: FBN2.
Skeletal dysplasia v2.87 FBN2 Sarah Leigh Tag Q2_21_MOI tag was added to gene: FBN2.
Arthrogryposis v3.95 FBN2 Sarah Leigh reviewed gene: FBN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arthrogryposis v3.95 FBN2 Sarah Leigh Publications for gene: FBN2 were set to 7493032; 33571691
Arthrogryposis v3.94 FBN2 Sarah Leigh Tag Q2_21_MOI tag was added to gene: FBN2.
Arthrogryposis v3.94 FBN2 Sarah Leigh Phenotypes for gene: FBN2 were changed from Contractural arachnodactyly, congenital 121050 to Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363
Arthrogryposis v3.93 FBN2 Sarah Leigh Publications for gene: FBN2 were set to 7493032
Inborn errors of metabolism v2.127 OPA1 Sarah Leigh Added comment: Comment on phenotypes: Optic atrophy plus syndrome, 125250;{Glaucoma, normal tension, susceptibility to}, 606657;Disorders of mitochondrial DNA maintenance and integrity;Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions;Optic atrophy 1, 165500;Mitochondrial DNA Depletion Syndrome;Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Inborn errors of metabolism v2.127 OPA1 Sarah Leigh Phenotypes for gene: OPA1 were changed from Optic atrophy plus syndrome, 125250; {Glaucoma, normal tension, susceptibility to}, 606657; Disorders of mitochondrial DNA maintenance and integrity; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions; Optic atrophy 1, 165500; Mitochondrial DNA Depletion Syndrome; Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) to ?Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type) OMIM:616896; mitochondrial DNA depletion syndrome 14 (cardioencephalomyopathic type) MONDO:0014820; Optic atrophy 1 OMIM:165500; autosomal dominant optic atrophy, classic form MONDO:0008134; Optic atrophy plus syndrome OMIM:125250; optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy MONDO:0007429; Behr syndrome OMIM:210000; Behr syndrome MONDO:0008858
Mitochondrial disorders v2.34 OPA1 Sarah Leigh Added comment: Comment on phenotypes: Disorders of mitochondrial DNA maintenance and integrity;{Glaucoma, normal tension, susceptibility to}, 606657
Mitochondrial disorders v2.34 OPA1 Sarah Leigh Phenotypes for gene: OPA1 were changed from Disorders of mitochondrial DNA maintenance and integrity; Optic atrophy 1, 165500; {Glaucoma, normal tension, susceptibility to}, 606657; Optic atrophy plus syndrome, 125250; Mitochondrial DNA Depletion Syndrome; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions; Optic atrophy 1, 165500 to ?Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type) OMIM:616896; mitochondrial DNA depletion syndrome 14 (cardioencephalomyopathic type) MONDO:0014820; Optic atrophy 1 OMIM:165500; autosomal dominant optic atrophy, classic form MONDO:0008134; Optic atrophy plus syndrome OMIM:125250; optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy MONDO:0007429; Behr syndrome OMIM:210000; Behr syndrome MONDO:0008858
Ataxia and cerebellar anomalies - narrow panel v2.149 OPA1 Sarah Leigh edited their review of gene: OPA1: Added comment: Associated with relevant phenotypes in OMIM and as confirmed Gen2Phen gene for Optic atrophy plus syndrome OMIM:125250 and a probable gene for Behr syndrome OMIM:210000. At least biallelic 11 variants reported in at least 10 unrelated cases (summarized in PMID 28494813, additional file 7).; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.149 OPA1 Sarah Leigh Tag Q2_21_rating tag was added to gene: OPA1.
Ataxia and cerebellar anomalies - narrow panel v2.149 OPA1 Sarah Leigh Classified gene: OPA1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.149 OPA1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.149 OPA1 Sarah Leigh Gene: opa1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.148 OPA1 Sarah Leigh Phenotypes for gene: OPA1 were changed from Optic atrophy plus syndrome, MIM# 125250 to Optic atrophy plus syndrome OMIM:125250; optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy MONDO:0007429; Behr syndrome OMIM:210000; Behr syndrome MONDO:0008858
Ataxia and cerebellar anomalies - narrow panel v2.147 OPA1 Sarah Leigh Publications for gene: OPA1 were set to 28494813; 27150940; 24970096; 11017079; 11017080; 17722006; 25012220
Inborn errors of metabolism v2.126 OPA1 Sarah Leigh Publications for gene: OPA1 were set to 27604308
Mitochondrial disorders v2.33 OPA1 Sarah Leigh Publications for gene: OPA1 were set to
Ataxia and cerebellar anomalies - narrow panel v2.146 OPA1 Sarah Leigh Publications for gene: OPA1 were set to 28494813
Ataxia and cerebellar anomalies - narrow panel v2.145 OPA1 Sarah Leigh Mode of inheritance for gene: OPA1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Holoprosencephaly v2.17 DISP1 Sarah Leigh Tag Q2_21_expert_review tag was added to gene: DISP1.
Holoprosencephaly v2.17 DISP1 Sarah Leigh Publications for gene: DISP1 were set to 27363716
White matter disorders and cerebral calcification - narrow panel v1.50 DEGS1 Eleanor Williams Classified gene: DEGS1 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.50 DEGS1 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber, but with a recommendation for green rating at the next GMS review. >3 cases reported with a plausible disease causing variant in DEGS1. Presentation is in young children.
White matter disorders and cerebral calcification - narrow panel v1.50 DEGS1 Eleanor Williams Gene: degs1 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v1.49 DEGS1 Eleanor Williams Tag Q2_21_rating tag was added to gene: DEGS1.
White matter disorders and cerebral calcification - narrow panel v1.49 DEGS1 Eleanor Williams Phenotypes for gene: DEGS1 were changed from Leukodystrophy, hypomyelinating, 18, MIM#618404 to Leukodystrophy, hypomyelinating, 18, OMIM:618404
White matter disorders and cerebral calcification - narrow panel v1.48 DEGS1 Eleanor Williams Publications for gene: DEGS1 were set to 30620338; 30620337
White matter disorders and cerebral calcification - narrow panel v1.47 DEGS1 Eleanor Williams reviewed gene: DEGS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30620338, 30620337, 31186544; Phenotypes: Leukodystrophy, hypomyelinating, 18, OMIM:618404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.641 FKBP8 Rhiannon Mellis reviewed gene: FKBP8: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 29261186; Phenotypes: Vertebral segmentation defects; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.144 OPA1 Sarah Leigh Mode of inheritance for gene: OPA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.143 NKX2-1 Sarah Leigh edited their review of gene: NKX2-1: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least five variants reported in unrelated cases of Choreoathetosis, hypothyroidism, and neonatal respiratory distress OMIM:610978.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.143 NKX2-1 Sarah Leigh Tag Q2_21_rating tag was added to gene: NKX2-1.
Ataxia and cerebellar anomalies - narrow panel v2.143 NKX2-1 Sarah Leigh Classified gene: NKX2-1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.143 NKX2-1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.143 NKX2-1 Sarah Leigh Gene: nkx2-1 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v1.47 DCAF17 Eleanor Williams Phenotypes for gene: DCAF17 were changed from Woodhouse-Sakati syndrome, MIM# 241080 to Woodhouse-Sakati syndrome, OMIM:241080
White matter disorders and cerebral calcification - narrow panel v1.46 DCAF17 Eleanor Williams Publications for gene: DCAF17 were set to 19026396; 20507343
White matter disorders and cerebral calcification - narrow panel v1.45 DCAF17 Eleanor Williams changed review comment from: Associated with Woodhouse-Sakati syndrome in OMIM (#241080 (AR))
DCAF17 is also known as C2ORF37

PMID: 19026396 - Alazami et al 2008 - report single bp deletion in C2orf37 in 8 families of Saudi origin (identified as a founder mutation). Patients phenotypes included hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome (Woodhouse-Sakati syndrome). 3 other variants were then found in patients of different ethnicities (another 1 bp deletion leading to a frameshift and 2 variants affecting splice donor sites). The variants segregated with the disease in all families. The two 1 bp changes are predicted to affect the beta isoform only.

PMID: 20507343 - Alazami et al 2010 - report 7 new patients from 4 families (3 ethnic backgrounds, Italian, French Gypsy and Turkish) who present with Woodhouse-Sakati syndrome. Each family had a different variant in C2orf37 - 3 nonsense mutations and a splice site ablation.

PMID: 30409855 - Abusrair et al 2018 - reviewed brain MR images of 26 patients with a clinical and genetic diagnosis of Woodhouse-Sakati syndrome. All participants had confirmed homozygous pathogenic variants in DCAF17. White matter lesions were observed in 18 patients (69.2%).; to: Associated with Woodhouse-Sakati syndrome in OMIM (#241080 (AR))
DCAF17 is also known as C2ORF37

PMID: 19026396 - Alazami et al 2008 - report single bp deletion in C2orf37 in 8 families of Saudi origin (identified as a founder mutation). Patients phenotypes included hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome (Woodhouse-Sakati syndrome). 3 other variants were then found in patients of different ethnicities (another 1 bp deletion leading to a frameshift and 2 variants affecting splice donor sites). The variants segregated with the disease in all families. The two 1 bp changes are predicted to affect the beta isoform only.

PMID: 20507343 - Alazami et al 2010 - report 7 new patients from 4 families (3 ethnic backgrounds, Italian, French Gypsy and Turkish) who present with Woodhouse-Sakati syndrome. Each family had a different variant in C2orf37 - 3 nonsense mutations and a splice site ablation.

PMID: 30409855 - Abusrair et al 2018 - reviewed brain MR images of 26 patients with a clinical and genetic diagnosis of Woodhouse-Sakati syndrome. All participants had confirmed homozygous pathogenic variants in DCAF17. White matter lesions were observed in 18 patients (69.2%).

PMID: 31726291 - Bohlega et al 2019 - report on 38 individuals from 17 families were identified as having a clinically and genetically confirmed diagnosis of WSS. All patients shared the same founder DCAF17: NM_001164821:exon4: c.436delC:p.L146fs frameshift deletion. Two groups identified based on phenotype. The age of onset of neurological symptoms for the group with the more severe phenotype was 12.6 ± 4.5 years (range, 9–17 years).
Ataxia and cerebellar anomalies - narrow panel v2.142 NKX2-1 Sarah Leigh Phenotypes for gene: NKX2-1 were changed from Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700 to Choreoathetosis, hypothyroidism, and neonatal respiratory distress OMIM; hereditary progressive chorea without dementia MONDO:0021011:610978; brain-lung-thyroid syndrome MONDO:0012593; Chorea, hereditary benign OMIM:118700
Ataxia and cerebellar anomalies - narrow panel v2.141 MVK Sarah Leigh edited their review of gene: MVK: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Mevalonic aciduria OMIM:610377. At least nine variants reported at least seven unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.141 MVK Sarah Leigh Tag Q2_21_rating tag was added to gene: MVK.
White matter disorders and cerebral calcification - narrow panel v1.45 DCAF17 Eleanor Williams Classified gene: DCAF17 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.45 DCAF17 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from grey to amber, but with a recommendation for green rating following GMS review. >3 cases of variants in DCAF17 in patients with Woodhouse-Sakati syndrome and white matter lesions observed in approx 70% of patients.
White matter disorders and cerebral calcification - narrow panel v1.45 DCAF17 Eleanor Williams Gene: dcaf17 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v1.44 DCAF17 Eleanor Williams Tag Q2_21_rating tag was added to gene: DCAF17.
Ataxia and cerebellar anomalies - narrow panel v2.141 MVK Sarah Leigh Publications for gene: MVK were set to 24896178; 26503795
Ataxia and cerebellar anomalies - narrow panel v2.140 MVK Sarah Leigh Added comment: Comment on phenotypes: Variants are associated with Hyper-IgD syndrome OMIM:260920 (biallelic) & Porokeratosis 3, multiple types OMIM:175900 (monoallelic).
Ataxia and cerebellar anomalies - narrow panel v2.140 MVK Sarah Leigh Phenotypes for gene: MVK were changed from Mevalonic aciduria 610377 to Mevalonic aciduria OMIM:610377; mevalonic aciduria MONDO:0012481
White matter disorders and cerebral calcification - narrow panel v1.44 DCAF17 Eleanor Williams reviewed gene: DCAF17: Rating: ; Mode of pathogenicity: None; Publications: 19026396, 20507343, 30409855; Phenotypes: Woodhouse-Sakati syndrome OMIM:241080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.139 MTFMT Sarah Leigh edited their review of gene: MTFMT: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least eight variants reported in at least eight unrelated cases of Combined oxidative phosphorylation deficiency 15 OMIM:614947.; Changed rating: GREEN
Intellectual disability v3.1041 PIGC Arina Puzriakova Classified gene: PIGC as Amber List (moderate evidence)
Intellectual disability v3.1041 PIGC Arina Puzriakova Added comment: Comment on list classification: There are now at least 3 unrelated families with biallelic variants in this gene, and severe DD/ID is evident in all cases (PMIDs: 27694521; 32707268) . Therefore, PIGC can be upgraded to Green status at the next GMS panel update.
Intellectual disability v3.1041 PIGC Arina Puzriakova Gene: pigc has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.139 MTFMT Sarah Leigh Tag Q2_21_rating tag was added to gene: MTFMT.
Ataxia and cerebellar anomalies - narrow panel v2.139 MTFMT Sarah Leigh Classified gene: MTFMT as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.139 MTFMT Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.139 MTFMT Sarah Leigh Gene: mtfmt has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.138 MTFMT Sarah Leigh Publications for gene: MTFMT were set to 26060307; 24461907
Intellectual disability v3.1040 PIGC Arina Puzriakova Phenotypes for gene: PIGC were changed from Glycosylphosphatidylinositol biosynthesis defect 16, 617816 to Glycosylphosphatidylinositol biosynthesis defect 16, OMIM:617816
Intellectual disability v3.1039 PIGC Arina Puzriakova Publications for gene: PIGC were set to 27694521
Ataxia and cerebellar anomalies - narrow panel v2.137 MTFMT Sarah Leigh Phenotypes for gene: MTFMT were changed from Combined oxidative phosphorylation deficiency 15 MIM#614947; Mitochondrial complex I deficiency, nuclear type 27 MIM#618248 to Combined oxidative phosphorylation deficiency 15 OMIM:614947; combined oxidative phosphorylation defect type 15 MONDO:0013987; Mitochondrial complex I deficiency, nuclear type 27 OMIM:618248; mitochondrial complex 1 deficiency, nuclear type 27 MONDO:0032631
Intellectual disability v3.1038 PIGC Arina Puzriakova Tag Q2_21_rating tag was added to gene: PIGC.
Mitochondrial disorders v2.32 MTFMT Sarah Leigh Added comment: Comment on phenotypes: Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Mitochondrial disorders v2.32 MTFMT Sarah Leigh Phenotypes for gene: MTFMT were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 15, 614947; Mitochondrial complex I deficiency, nuclear type 27 618248 to Combined oxidative phosphorylation deficiency 15 OMIM:614947; combined oxidative phosphorylation defect type 15 MONDO:0013987; Mitochondrial complex I deficiency, nuclear type 27 OMIM:618248; mitochondrial complex 1 deficiency, nuclear type 27 MONDO:0032631
Genetic epilepsy syndromes v2.330 PIGC Arina Puzriakova Phenotypes for gene: PIGC were changed from Glycosylphosphatidylinositol biosynthesis defect 16, 617816 to Glycosylphosphatidylinositol biosynthesis defect 16, OMIM:617816
Genetic epilepsy syndromes v2.329 PIGC Arina Puzriakova Publications for gene: PIGC were set to
Genetic epilepsy syndromes v2.328 PIGC Arina Puzriakova reviewed gene: PIGC: Rating: GREEN; Mode of pathogenicity: None; Publications: 32707268; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 16, OMIM:617816; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1038 PIGC Arina Puzriakova reviewed gene: PIGC: Rating: GREEN; Mode of pathogenicity: None; Publications: 32707268; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 16, OMIM:617816; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe Paediatric Disorders v1.76 MTFMT Sarah Leigh Phenotypes for gene: MTFMT were changed from Mitochondrial complex I deficiency, nuclear type 27, 618248; Combined oxidative phosphorylation deficiency 15, 614947 to Combined oxidative phosphorylation deficiency 15 OMIM:614947; combined oxidative phosphorylation defect type 15 MONDO:0013987; Mitochondrial complex I deficiency, nuclear type 27 OMIM:618248; mitochondrial complex 1 deficiency, nuclear type 27 MONDO:0032631
Childhood onset dystonia or chorea or related movement disorder v1.91 MTFMT Sarah Leigh Phenotypes for gene: MTFMT were changed from Combined oxidative phosphorylation deficiency 15, 614947; Mitochondrial complex I deficiency, nuclear type 27, 618248 to Combined oxidative phosphorylation deficiency 15 OMIM:614947; combined oxidative phosphorylation defect type 15 MONDO:0013987; Mitochondrial complex I deficiency, nuclear type 27 OMIM:618248; mitochondrial complex 1 deficiency, nuclear type 27 MONDO:0032631
Intellectual disability v3.1038 MTFMT Sarah Leigh Phenotypes for gene: MTFMT were changed from Combined oxidative phosphorylation deficiency 15, 614947 to Combined oxidative phosphorylation deficiency 15 OMIM:614947; combined oxidative phosphorylation defect type 15 MONDO:0013987; Mitochondrial complex I deficiency, nuclear type 27 OMIM:618248; mitochondrial complex 1 deficiency, nuclear type 27 MONDO:0032631
Inborn errors of metabolism v2.125 MTFMT Sarah Leigh Phenotypes for gene: MTFMT were changed from Combined oxidative phosphorylation deficiency 15 614947; Mitochondrial complex I deficiency, nuclear type 27 618248 to Combined oxidative phosphorylation deficiency 15 OMIM:614947; combined oxidative phosphorylation defect type 15 MONDO:0013987; Mitochondrial complex I deficiency, nuclear type 27 OMIM:618248; mitochondrial complex 1 deficiency, nuclear type 27 MONDO:0032631
Possible mitochondrial disorder - nuclear genes v1.41 MTFMT Sarah Leigh Phenotypes for gene: MTFMT were changed from Combined oxidative phosphorylation deficiency 15, 614947; Mitochondrial complex I deficiency, nuclear type 27, 618248 to Combined oxidative phosphorylation deficiency 15 OMIM:614947; combined oxidative phosphorylation defect type 15 MONDO:0013987; Mitochondrial complex I deficiency, nuclear type 27 OMIM:618248; mitochondrial complex 1 deficiency, nuclear type 27 MONDO:0032631
Inherited white matter disorders v1.91 MTFMT Sarah Leigh Phenotypes for gene: MTFMT were changed from Combined oxidative phosphorylation deficiency 15; 614947; 22499348; 23499752 to Combined oxidative phosphorylation deficiency 15 OMIM:614947; combined oxidative phosphorylation defect type 15 MONDO:0013987; Mitochondrial complex I deficiency, nuclear type 27 OMIM:618248; mitochondrial complex 1 deficiency, nuclear type 27 MONDO:0032631
Primary immunodeficiency v2.419 MPEG1 Arina Puzriakova Phenotypes for gene: MPEG1 were changed from Immunodeficiency 77, MIM# 619223 to Immunodeficiency 77, OMIM:619223
Primary immunodeficiency v2.418 MPEG1 Arina Puzriakova Classified gene: MPEG1 as Amber List (moderate evidence)
Primary immunodeficiency v2.418 MPEG1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Sufficient number of unrelated cases (5 - PMIDs: 33224153; 28422754) with immunopathology and distinct biallelic variants in this gene to rate as Green at the next GMS panel update. Supported by functional evidence and animal model.

MPEG1 is also associated with a relevant phenotype in OMIM (MIM# 619223)
Primary immunodeficiency v2.418 MPEG1 Arina Puzriakova Gene: mpeg1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency v2.417 MPEG1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: MPEG1.
Intestinal failure v1.36 IL37 Arina Puzriakova gene: IL37 was added
gene: IL37 was added to Intestinal failure. Sources: Literature
Mode of inheritance for gene: IL37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL37 were set to 33674380
Phenotypes for gene: IL37 were set to Infantile inflammatory bowel disease
Review for gene: IL37 was set to RED
Added comment: Single family reported with homozygous truncating variant this gene and infantile-onset of IBD, some functional data.
Sources: Literature
Primary immunodeficiency v2.417 IL37 Arina Puzriakova Classified gene: IL37 as Red List (low evidence)
Primary immunodeficiency v2.417 IL37 Arina Puzriakova Added comment: Comment on list classification: Rating Red awaiting further evidence, as only a single case reported to date (PMID: 33674380)
Primary immunodeficiency v2.417 IL37 Arina Puzriakova Gene: il37 has been classified as Red List (Low Evidence).
Hereditary spastic paraplegia - adult onset v1.17 CYP2U1 Sarah Leigh changed review comment from: The Q2_21_expert_review tag has been added to this gene as there is a conflict of opinion of the rating of CYP2U1 on the this - Hereditary spastic paraplegia - adult onset, as variants in CYP2U1 are usually associated with Spastic paraplegia 56, autosomal recessive OMIM:615030 in childhood. The green rating may be justified to ensure that edge cases may be identified.
GMS opinion is sort on this issue.; to: The Q2_21_expert_review tag has been added to this gene as there is a conflict of opinion of the rating of CYP2U1 on the Hereditary spastic paraplegia - adult onset panel, as variants in CYP2U1 are usually associated with Spastic paraplegia 56, autosomal recessive OMIM:615030 in childhood. The green rating may be justified to ensure that edge cases may be identified.
GMS opinion is sort on this issue.
Hereditary spastic paraplegia - adult onset v1.17 CYP2U1 Sarah Leigh reviewed gene: CYP2U1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary spastic paraplegia - adult onset v1.17 CYP2U1 Sarah Leigh Tag Q2_21_expert_review tag was added to gene: CYP2U1.
Ataxia and cerebellar anomalies - narrow panel v2.136 ADPRHL2 Sarah Leigh Tag Q2_21_rating tag was added to gene: ADPRHL2.
Hereditary ataxia - adult onset v2.42 ADPRHL2 Sarah Leigh changed review comment from: The Q2_21_expert_review tag has been added to this gene as there is a conflict of opinion of the rating of ADPRHL2 on the this - Hereditary ataxia - adult onset - panel, as variants in ADPRHL2 are usually associated with Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 in infancy or in childhood. The green rating may be justifyied inorder to ensure that edge cases may be identified.
GMS opinion is sort on this issue.; to: The Q2_21_expert_review tag has been added to this gene as there is a conflict of opinion of the rating of ADPRHL2 on the this - Hereditary ataxia - adult onset - panel, as variants in ADPRHL2 are usually associated with Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 in infancy or in childhood. The green rating may be justified to ensure that edge cases may be identified.
GMS opinion is sort on this issue.
Hereditary ataxia - adult onset v2.42 ADPRHL2 Sarah Leigh changed review comment from: The Q2_21_expert_review has been added to this gene as there is a conflict of opinion of the rating of this ADPRHL2 on the this - Hereditary ataxia - adult onset - panel, as variants in ADPRHL2 are usually associated with Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 in infancy or in childhood.
GMS opinion is sort on this issue.; to: The Q2_21_expert_review tag has been added to this gene as there is a conflict of opinion of the rating of ADPRHL2 on the this - Hereditary ataxia - adult onset - panel, as variants in ADPRHL2 are usually associated with Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 in infancy or in childhood. The green rating may be justifyied inorder to ensure that edge cases may be identified.
GMS opinion is sort on this issue.
Hereditary ataxia - adult onset v2.42 ADPRHL2 Sarah Leigh changed review comment from: The Q2_21_expert_review has been added to this gene as there is a conflict of opinion of the rating of this ADPRHL2 on the this - Hereditary ataxia - adult onset - panel.as variants in ADPRHL2 are usually associated with Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 in infancy or in childhood.
GMS opinion is sort on this issue.; to: The Q2_21_expert_review has been added to this gene as there is a conflict of opinion of the rating of this ADPRHL2 on the this - Hereditary ataxia - adult onset - panel, as variants in ADPRHL2 are usually associated with Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 in infancy or in childhood.
GMS opinion is sort on this issue.
Hereditary ataxia - adult onset v2.42 ADPRHL2 Sarah Leigh reviewed gene: ADPRHL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary ataxia - adult onset v2.42 ADPRHL2 Sarah Leigh Tag Q2_21_expert_review tag was added to gene: ADPRHL2.
Ataxia and cerebellar anomalies - narrow panel v2.136 EEF2 Eleanor Williams Classified gene: EEF2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.136 EEF2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber on advice of Genomics England clinical team. Amber rating selected pending further cases and delineation of the phenotype
Ataxia and cerebellar anomalies - narrow panel v2.136 EEF2 Eleanor Williams Gene: eef2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.135 EEF2 Eleanor Williams gene: EEF2 was added
gene: EEF2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: EEF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EEF2 were set to 23001565; 33355653
Phenotypes for gene: EEF2 were set to Spinocerebellar ataxia 26 OMIM:609306
Review for gene: EEF2 was set to AMBER
Added comment: Provisionally associated with ?Spinocerebellar ataxia 26 #609306 (AD) in OMIM based on Hekman et al 2012 case.

PMID: 23001565 - Hekman et al 2012 - report a six-generation kindred of Norwegian ancestry with a late-onset pure cerebellar ataxia in which a heterozygous P596H substitution in eEF2 was found to segregate with the disease phenotype in 24 individuals and two currently asymptomatic individuals. Functional studies in yeast showed that the variant (P580H in the EFT2 gene in yeast) affected translational fidelity.

PMID: 33355653 - Nabais Sá et al 2021 - identified de novo EEF2 missense variants in 3 unrelated children (3, 6 and 9 years of age) with a mild phenotype comprising motor delay and relative macrocephaly associated with ventriculomegaly.
Sources: Literature
Hereditary ataxia - adult onset v2.42 EEF2 Eleanor Williams Classified gene: EEF2 as Amber List (moderate evidence)
Hereditary ataxia - adult onset v2.42 EEF2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber on advice of Genomics England clinical team. Amber rating selected pending further cases and delineation of the phenotype
Hereditary ataxia - adult onset v2.42 EEF2 Eleanor Williams Gene: eef2 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia - adult onset v2.41 EEF2 Eleanor Williams gene: EEF2 was added
gene: EEF2 was added to Hereditary ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: EEF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EEF2 were set to 23001565; 33355653
Phenotypes for gene: EEF2 were set to Spinocerebellar ataxia 26 OMIM:609306
Review for gene: EEF2 was set to AMBER
Added comment: Provisionally associated with ?Spinocerebellar ataxia 26 #609306 (AD) in OMIM based on Hekman et al 2012 case.

PMID: 23001565 - Hekman et al 2012 - report a six-generation kindred of Norwegian ancestry with a late-onset pure cerebellar ataxia in which a heterozygous P596H substitution in eEF2 was found to segregate with the disease phenotype in 24 individuals and two currently asymptomatic individuals. Functional studies in yeast showed that the variant (P580H in the EFT2 gene in yeast) affected translational fidelity.

PMID: 33355653 - Nabais Sá et al 2021 - identified de novo EEF2 missense variants in 3 unrelated children (3, 6 and 9 years of age) with a mild phenotype comprising motor delay and relative macrocephaly associated with ventriculomegaly.
Sources: Literature
Lipodystrophy - childhood onset v2.9 OTULIN Zornitza Stark gene: OTULIN was added
gene: OTULIN was added to Lipodystrophy - childhood onset. Sources: Expert Review
Mode of inheritance for gene: OTULIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OTULIN were set to 27523608; 27559085
Phenotypes for gene: OTULIN were set to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099
Review for gene: OTULIN was set to GREEN
gene: OTULIN was marked as current diagnostic
Added comment: Autoinflammatory disease characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy. Additional features may include diarrhea, increased serum C-reactive protein, leukocytosis, and neutrophilia in the absence of any infection.

At least 3 unrelated families reported.
Sources: Expert Review
Lipodystrophy - childhood onset v2.9 KCNJ6 Zornitza Stark gene: KCNJ6 was added
gene: KCNJ6 was added to Lipodystrophy - childhood onset. Sources: Expert Review
Mode of inheritance for gene: KCNJ6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ6 were set to 25620207; 29852244
Phenotypes for gene: KCNJ6 were set to Keppen-Lubinsky syndrome, MIM# 614098; MONDO:0013572
Review for gene: KCNJ6 was set to GREEN
gene: KCNJ6 was marked as current diagnostic
Added comment: Keppen-Lubinsky syndrome characterised by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth.

Four unrelated individuals reported with de novo variants in this gene (one recurred in 2), mouse model. One of the individuals did not have lipodystrophy but had a prominent hyperkinetic movement disorder.
Sources: Expert Review
Lipodystrophy - childhood onset v2.9 FBN1 Zornitza Stark gene: FBN1 was added
gene: FBN1 was added to Lipodystrophy - childhood onset. Sources: Expert Review
Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBN1 were set to 20979188; 21594992; 21594993; 24613577; 26860060; 29666143
Phenotypes for gene: FBN1 were set to Marfan lipodystrophy syndrome, MIM# 616914
Review for gene: FBN1 was set to GREEN
gene: FBN1 was marked as current diagnostic
Added comment: The marfanoid-progeroid-lipodystrophy syndrome (MFLS) is characterized by congenital lipodystrophy, premature birth with an accelerated linear growth disproportionate to weight gain, and progeroid appearance with distinct facial features, including proptosis, downslanting palpebral fissures, and retrognathia. Other characteristic features include arachnodactyly, digital hyperextensibility, myopia, dural ectasia, and normal psychomotor development.

This specific phenotype is caused by variants occurring in or affecting exon 64.

More than 5 unrelated individuals reported, rabbit model.
Sources: Expert Review
Primary immunodeficiency v2.416 ZNFX1 Arina Puzriakova Classified gene: ZNFX1 as Amber List (moderate evidence)
Primary immunodeficiency v2.416 ZNFX1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Boaz Palterer. Sufficient number of unrelated cases (10 - PMIDs: 33876776; 33872655) with immunopathology and biallelic variants in this gene to rate as Green at the next GMS panel update.
Primary immunodeficiency v2.416 ZNFX1 Arina Puzriakova Gene: znfx1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency v2.415 ZNFX1 Arina Puzriakova Publications for gene: ZNFX1 were set to
Primary immunodeficiency v2.414 ZNFX1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: ZNFX1.
Primary immunodeficiency v2.414 ZNFX1 Arina Puzriakova reviewed gene: ZNFX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33876776, 33872655; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.134 CYP2U1 Sarah Leigh changed review comment from: Comment on phenotypes: Autosomal recessive spastic paraplegia 56 (#615030) complex form of disorder, ataxia not yet identified in affected patients.; to: Comment on phenotypes: Autosomal recessive spastic paraplegia 56 (#615030) is a complex form of disorder, ataxia not yet identified in affected patients (Table 1 in PMID: 27292318 provides a review of cases reported so far).
Ataxia and cerebellar anomalies - narrow panel v2.134 CYP2U1 Sarah Leigh Tag Q2_21_expert_review tag was added to gene: CYP2U1.
Intellectual disability v3.1037 JMJD1C Zornitza Stark gene: JMJD1C was added
gene: JMJD1C was added to Intellectual disability. Sources: Expert Review
Mode of inheritance for gene: JMJD1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: JMJD1C were set to 26181491; 32996679
Phenotypes for gene: JMJD1C were set to Intellectual disability
Review for gene: JMJD1C was set to GREEN
gene: JMJD1C was marked as current diagnostic
Added comment: Reported in ID cohort (with Rett-like phenotypic overlap) with supporting functional studies (PMID: 26181491). 7 individuals with rare variants identified, and variants demonstrated to be de novo in 2, one with a Rett-like phenotype and the other with ID. Functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. JMJD1C protein shown to be widely expressed in brain regions and that its depletion compromised dendritic activity.

Splice-disrupting JMJD1C variant reported in association with learning disability and myoclonic epilepsy (PMID 32996679).

Disruption of gene due to balanced translocation (PMID 33591602) implicated in autism spectrum disease phenotype.
Sources: Expert Review
Primary immunodeficiency v2.414 SYK Arina Puzriakova Tag Q2_21_rating tag was added to gene: SYK.
Primary immunodeficiency v2.414 SYK Arina Puzriakova Classified gene: SYK as Amber List (moderate evidence)
Primary immunodeficiency v2.414 SYK Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - PMID:33782605 report distinct monoallelic GoF variants in 5 families (6 individuals) with immune dysregulation and inflammation. Expression of one of these variants in a mouse model replicated aspects of the human immunopathology.
Primary immunodeficiency v2.414 SYK Arina Puzriakova Gene: syk has been classified as Amber List (Moderate Evidence).
Holoprosencephaly v2.16 DISP1 Zornitza Stark reviewed gene: DISP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 19184110, 26748417, 23542665; Phenotypes: Holoprosencephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Haematological malignancies for rare disease v1.1 RAD51 Zornitza Stark reviewed gene: RAD51: Rating: GREEN; Mode of pathogenicity: None; Publications: 30907510; Phenotypes: Fanconi anemia, complementation group R 617244; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare multisystem ciliopathy disorders v1.142 LAMA1 Sarah Leigh reviewed gene: LAMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.1037 LAMA1 Sarah Leigh reviewed gene: LAMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.134 LAMA1 Sarah Leigh edited their review of gene: LAMA1: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least five variants reported in at least three unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.134 LAMA1 Sarah Leigh Tag Q2_21_rating tag was added to gene: LAMA1.
Intellectual disability v3.1037 LAMA1 Sarah Leigh Phenotypes for gene: LAMA1 were changed from CEREBELLAR DYSPLASIA WITH CYSTS WITH OR WITHOUT RETINAL DYSTROPHY to Poretti-Boltshauser syndrome OMIM:615960; ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome MONDO:0014419
Rare multisystem ciliopathy disorders v1.142 LAMA1 Sarah Leigh Phenotypes for gene: LAMA1 were changed from cerebellar cysts; myopia; cerebellar vermis hypoplasia; gaze palsy; retinitis pigments to Poretti-Boltshauser syndrome OMIM:615960; ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome MONDO:0014419
Intellectual disability v3.1036 LAMA1 Sarah Leigh Publications for gene: LAMA1 were set to 21937992; 30244536
Rare multisystem ciliopathy disorders v1.141 LAMA1 Sarah Leigh Publications for gene: LAMA1 were set to https://www.ncbi.nlm.nih.gov/pubmed/25105227
Rare multisystem ciliopathy disorders v1.140 LAMA1 Sarah Leigh Classified gene: LAMA1 as Green List (high evidence)
Rare multisystem ciliopathy disorders v1.140 LAMA1 Sarah Leigh Gene: lama1 has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.134 LAMA1 Sarah Leigh Phenotypes for gene: LAMA1 were changed from Cerebellar ataxia, intellectual disability, oculomotor apraxia, cerebellar cysts; Poretti Boltshauser syndrome MIM#615960 to Poretti-Boltshauser syndrome OMIM:615960; ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome MONDO:0014419
Ataxia and cerebellar anomalies - narrow panel v2.133 LAMA1 Sarah Leigh Classified gene: LAMA1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.133 LAMA1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.133 LAMA1 Sarah Leigh Gene: lama1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.132 KCNA2 Sarah Leigh edited their review of gene: KCNA2: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least four variants reported in numberous cases, together with supportive functional studies, demonstrating GOF and LOF mechanisms.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.132 KCNA2 Sarah Leigh Classified gene: KCNA2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.132 KCNA2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.132 KCNA2 Sarah Leigh Gene: kcna2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.131 KCNA2 Sarah Leigh Tag Q2_21_rating tag was added to gene: KCNA2.
Ataxia and cerebellar anomalies - narrow panel v2.131 KCNA2 Sarah Leigh Mode of pathogenicity for gene: KCNA2 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
Genetic epilepsy syndromes v2.328 KCNA2 Sarah Leigh Added comment: Comment on mode of pathogenicity: Both dominant negative variants that result in LOF effect (RCV000170511, rs786205231) and GOF variants (rs786205231, rs786205232) have been associated with Developmental and epileptic encephalopathy 32 OMIM:616366
Genetic epilepsy syndromes v2.328 KCNA2 Sarah Leigh Mode of pathogenicity for gene: KCNA2 was changed from None to None
Hereditary ataxia v1.216 EEF2 Eleanor Williams Classified gene: EEF2 as Amber List (moderate evidence)
Hereditary ataxia v1.216 EEF2 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber on advice of Genomics England clinical team. Amber rating selected pending further cases and delineation of the phenotype
Hereditary ataxia v1.216 EEF2 Eleanor Williams Gene: eef2 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v2.327 KCNA2 Sarah Leigh Phenotypes for gene: KCNA2 were changed from Epileptic encephalopathy, early infantile, 32; EPILEPTIC ENCEPHALOPATHY to Developmental and epileptic encephalopathy 32 OMIM:616366; developmental and epileptic encephalopathy, 32 MONDO:0014607
Ataxia and cerebellar anomalies - narrow panel v2.130 KCNA2 Sarah Leigh Phenotypes for gene: KCNA2 were changed from Early infantile encephalopathy 32, MIM#616366 to Developmental and epileptic encephalopathy 32 OMIM:616366; developmental and epileptic encephalopathy, 32 MONDO:0014607
Ataxia and cerebellar anomalies - narrow panel v2.129 KCNA2 Sarah Leigh Added comment: Comment on mode of pathogenicity: Both dominant negative variants that result in LOF effect (RCV000170511, rs786205231) and GOF variants (rs786205231, rs786205232) have been associated with Developmental and epileptic encephalopathy 32 OMIM:616366
Ataxia and cerebellar anomalies - narrow panel v2.129 KCNA2 Sarah Leigh Mode of pathogenicity for gene: KCNA2 was changed from None to None
Intellectual disability v3.1035 NEUROD2 Arina Puzriakova Classified gene: NEUROD2 as Amber List (moderate evidence)
Intellectual disability v3.1035 NEUROD2 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene as Green at the next GMS panel update - sufficient number of unrelated cases (4, plus 1 unpublished), all presenting GDD as an early feature. Particularly pertinent to less severely affected individuals who do not develop seizures.
Intellectual disability v3.1035 NEUROD2 Arina Puzriakova Gene: neurod2 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v2.326 KCNA2 Sarah Leigh Publications for gene: KCNA2 were set to Syrbe et al (2015) Nat Genet 47(4): 393-9
Ataxia and cerebellar anomalies - narrow panel v2.128 KCNA2 Sarah Leigh Publications for gene: KCNA2 were set to 29050392
Intellectual disability v3.1034 NEUROD2 Arina Puzriakova gene: NEUROD2 was added
gene: NEUROD2 was added to Intellectual disability. Sources: Literature
Q2_21_rating tags were added to gene: NEUROD2.
Mode of inheritance for gene: NEUROD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NEUROD2 were set to 16504944; 30323019; 33438828
Phenotypes for gene: NEUROD2 were set to Developmental and epileptic encephalopathy 72, OMIM:618374
Review for gene: NEUROD2 was set to GREEN
Added comment: NEUROD2 is associated with a relevant phenotype in OMIM (MIM# 618374), but is not yet listed in Gene2Phenotype.

- PMID: 30323019 (2019) - Two unrelated children with refractory early-infantile epileptic encephalopathy. Developmental delay (DD) preceded onset of seizures in both cases, with signs of DD becoming evident at 2-4 months and seizures arising at 5 months of age. Patient 1 became seizure-free after introducing a ketogenic diet at 16 months; however, an EEG at 22 months remained abnormal and she continues to have severe GDD with no independent sitting, walking or speaking at the chronological age of 3 years and 2 months. Patient 2 became seizure-free when a vagal nerve stimulator (VNS) was placed at 16 months of age. He displayed significant improvement on EEG and subsequently began regaining neurodevelopmental milestones.
WES revealed different de novo variants in the NEUROD2 gene (P1: c.388G>C, p.E130Q; P2: c.401T>C, p.M134T, respectively). Knockdown of the neurod2 in Xenopus tropicalis tadpoles resulted in abnormal swimming behaviour and progressive seizures followed by periods of immobility. Overexpression of wild-type human NEUROD2 in tadpoles induced non-neuronal cells to differentiate into neurons - on the other hand, overexpression of the mutant alleles failed to to cause any (p.E130Q) or a comparable degree (p.M134T) of ectopic neuronal induction as seen with the wild-type protein.

- Conference poster (Genomics of Rare Disease 2021) - 'Neuronal Differentiation Factor 2 (NEUROD2) Pathogenic Variant as a Molecular Aetiology of Infantile Spasm ' by Sakpichaisakul et al, QSNICH, Thailand -
In a 15 month-old female with infantile spasm, trio exome sequencing revealed a de novo variant in NEUROD2 (c.388G>C, p.E130Q). She was born of non-consanguineous healthy parents with no family history of epilepsy. Poor eye contact and no social smile were noted in the first few months, followed by the first infantile spasm at 5 months of age. This was initially controlled by combined vigabatrin and prednisolone therapy - however relapsing seizures were detected at 15 months. Sequential treatment with vigabatrin following prednisolone resulted in cessation of seizures, and subsequently regaining of neurodevelopmental milestones (sitting without support, grabbing objects without pincer grasp and speaking one single word)

----- Cases without seizures -

- PMID: 33438828 (2021) - Adolescent (14 yrs old) with GDD but without seizures who was found to have a novel de novo NEUROD2 missense variant (c.488 T > C, p.L163P). An additional individual (12 yrs) with DD and a different missense NEUROD2 (c.703G>A, p.A235T) was also identified, but lacking parental samples for segregation analysis.
Functional analysis in Xenopus laevis revealed that injection of the p.L163P mRNA variant resulted in a defective ability to induce ectopic neurons in tadpoles as compared with wild-type NEUROD2 mRNA, while the p.A235T variant functioned similarly to wild-type.
Sources: Literature
Genetic epilepsy syndromes v2.325 NEUROD2 Arina Puzriakova changed review comment from: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 2 cases in literature (plus 1 unpublished case) with infantile seizures and heterozygous variants in this gene, supported by animal models.

Associated with relevant phenotype in OMIM (MIM# 618374) but not yet listed in Gene2Phenotype.; to: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 2 cases in literature (plus 1 unpublished case) with infantile seizures and heterozygous variants in this gene, supported by animal models.
Genomic imprinting v0.98 NLRP2 Sarah Leigh Publications for gene: NLRP2 were set to 19300480; 30221575; 32169557; 28422141; 28317850
Genetic epilepsy syndromes v2.325 NEUROD2 Arina Puzriakova Classified gene: NEUROD2 as Amber List (moderate evidence)
Genetic epilepsy syndromes v2.325 NEUROD2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 2 cases in literature (plus 1 unpublished case) with infantile seizures and heterozygous variants in this gene, supported by animal models.

Associated with relevant phenotype in OMIM (MIM# 618374) but not yet listed in Gene2Phenotype.
Genetic epilepsy syndromes v2.325 NEUROD2 Arina Puzriakova Gene: neurod2 has been classified as Amber List (Moderate Evidence).
Growth failure in early childhood v1.62 NLRP2 Sarah Leigh Publications for gene: NLRP2 were set to 26323243; 29574422
Genetic epilepsy syndromes v2.324 NEUROD2 Arina Puzriakova Tag Q2_21_rating tag was added to gene: NEUROD2.
Genetic epilepsy syndromes v2.324 NEUROD2 Arina Puzriakova edited their review of gene: NEUROD2: Added comment: - Conference poster (Genomics of Rare Disease 2021) - 'Neuronal Differentiation Factor 2 (NEUROD2) Pathogenic Variant as a Molecular Aetiology of Infantile Spasm ' by Sakpichaisakul et al, QSNICH, Thailand -
In a 15 month-old female with infantile spasm, trio exome sequencing revealed a de novo variant in NEUROD2 (c.388G>C, p.E130Q). She was born of non-consanguineous healthy parents with no family history of epilepsy. Poor eye contact and no social smile were noted in the first few months, followed by the first infantile spasm at 5 months of age. This was initially controlled by combined vigabatrin and prednisolone therapy - however relapsing seizures were detected at 15 months. Sequential treatment with vigabatrin following prednisolone resulted in cessation of seizures, and subsequently regaining of neurodevelopmental milestones (sitting without support, grabbing objects without pincer grasp and speaking one single word); Changed rating: GREEN
Growth failure in early childhood v1.61 NLRP7 Sarah Leigh Added comment: Comment on mode of inheritance: Review from Eamonn Maher: I think it would be better that these are maternal effect genes for which biallelic variants in a healthy women cause a reproductive phenotype that may include miscarriage, hydatidiform mole or children with a congenital imprinting disorder
Growth failure in early childhood v1.61 NLRP7 Sarah Leigh Mode of inheritance for gene: NLRP7 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
Growth failure in early childhood v1.60 PADI6 Sarah Leigh Added comment: Comment on mode of inheritance: Review from Eamonn Maher: I think it would be better that these are maternal effect genes for which biallelic variants in a healthy women cause a reproductive phenotype that may include miscarriage, hydatidiform mole or children with a congenital imprinting disorder
Growth failure in early childhood v1.60 PADI6 Sarah Leigh Mode of inheritance for gene: PADI6 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
Genomic imprinting v0.97 PADI6 Sarah Leigh Added comment: Comment on mode of inheritance: Review from Eamonn Maher: I think it would be better that these are maternal effect genes for which biallelic variants in a healthy women cause a reproductive phenotype that may include miscarriage, hydatidiform mole or children with a congenital imprinting disorder
Genomic imprinting v0.97 PADI6 Sarah Leigh Mode of inheritance for gene: PADI6 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
Genomic imprinting v0.96 NLRP7 Sarah Leigh Added comment: Comment on mode of inheritance: Review from Eamonn Maher: I think it would be better that these are maternal effect genes for which biallelic variants in a healthy women cause a reproductive phenotype that may include miscarriage, hydatidiform mole or children with a congenital imprinting disorder
Genomic imprinting v0.96 NLRP7 Sarah Leigh Mode of inheritance for gene: NLRP7 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
Genomic imprinting v0.95 NLRP5 Sarah Leigh Added comment: Comment on mode of inheritance: Review from Eamonn Maher: I think it would be better that these are maternal effect genes for which biallelic variants in a healthy women cause a reproductive phenotype that may include miscarriage, hydatidiform mole or children with a congenital imprinting disorder
Genomic imprinting v0.95 NLRP5 Sarah Leigh Mode of inheritance for gene: NLRP5 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
Growth failure in early childhood v1.59 NLRP5 Sarah Leigh changed review comment from: Comment on mode of inheritance: Comment from Eamonn Maher: I think it would be better that these are maternal effect genes for which biallelic variants in a healthy women cause a reproductive phenotype that may include miscarriage, hydatidiform mole or children with a congenital imprinting disorder; to: Comment on mode of inheritance: Review from Eamonn Maher: I think it would be better that these are maternal effect genes for which biallelic variants in a healthy women cause a reproductive phenotype that may include miscarriage, hydatidiform mole or children with a congenital imprinting disorder
Growth failure in early childhood v1.59 NLRP5 Sarah Leigh Added comment: Comment on mode of inheritance: Comment from Eamonn Maher: I think it would be better that these are maternal effect genes for which biallelic variants in a healthy women cause a reproductive phenotype that may include miscarriage, hydatidiform mole or children with a congenital imprinting disorder
Growth failure in early childhood v1.59 NLRP5 Sarah Leigh Mode of inheritance for gene: NLRP5 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
Ataxia and cerebellar anomalies - narrow panel v2.127 EXOSC1 Sarah Leigh Added comment: Comment on phenotypes: No phenotype in OMIM or in MONDO (21/04/2021)
Ataxia and cerebellar anomalies - narrow panel v2.127 EXOSC1 Sarah Leigh Phenotypes for gene: EXOSC1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia
Ataxia and cerebellar anomalies - narrow panel v2.126 EXOSC1 Sarah Leigh Classified gene: EXOSC1 as Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v2.126 EXOSC1 Sarah Leigh Added comment: Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one biallelic variant reported.
Ataxia and cerebellar anomalies - narrow panel v2.126 EXOSC1 Sarah Leigh Gene: exosc1 has been classified as Red List (Low Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.125 EXOSC1 Sarah Leigh Added comment: Comment on phenotypes: No phenotype listed in OMIM or in MONDO (21/04/2021)
Ataxia and cerebellar anomalies - narrow panel v2.125 EXOSC1 Sarah Leigh Phenotypes for gene: EXOSC1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia
Ataxia and cerebellar anomalies - narrow panel v2.124 EXOSC1 Sarah Leigh Classified gene: EXOSC1 as Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v2.124 EXOSC1 Sarah Leigh Added comment: Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one biallelic variant reported (PMID 33463720).
Ataxia and cerebellar anomalies - narrow panel v2.124 EXOSC1 Sarah Leigh Gene: exosc1 has been classified as Red List (Low Evidence).
Inborn errors of metabolism v2.124 NDUFB7 Sarah Leigh Added comment: Comment on phenotypes: No OMIM or MONDO phenotype (21/4/2021)
Inborn errors of metabolism v2.124 NDUFB7 Sarah Leigh Phenotypes for gene: NDUFB7 were changed from No OMIM phenotype; Isolated complex I deficiency to Congenital lactic acidosis; hypertrophic cardiomyopathy
Mitochondrial disorders v2.31 NDUFB7 Sarah Leigh Added comment: Comment on phenotypes: No OMIM or MONDO phenotype (21/4/2021)
Mitochondrial disorders v2.31 NDUFB7 Sarah Leigh Phenotypes for gene: NDUFB7 were changed from Isolated complex I deficiency; No OMIM phenotype to Congenital lactic acidosis; hypertrophic cardiomyopathy
Inborn errors of metabolism v2.123 NDUFB7 Sarah Leigh Mode of inheritance for gene: NDUFB7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Inborn errors of metabolism v2.122 NDUFB7 Sarah Leigh Tag watchlist tag was added to gene: NDUFB7.
Mitochondrial disorder with complex I deficiency v1.13 NDUFB7 Sarah Leigh Added comment: Comment on phenotypes: No OMIM or MONDO phenotype (21/4/2021)
Mitochondrial disorder with complex I deficiency v1.13 NDUFB7 Sarah Leigh Phenotypes for gene: NDUFB7 were changed from No OMIM phenotype to Congenital lactic acidosis; hypertrophic cardiomyopathy
Inborn errors of metabolism v2.122 NDUFB7 Sarah Leigh Classified gene: NDUFB7 as Amber List (moderate evidence)
Inborn errors of metabolism v2.122 NDUFB7 Sarah Leigh Added comment: Comment on list classification: Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one biallelic splicing variant reported. RNA sequencing revealed that this variant disrupted normal splicing (PMID 33502047) and human knock-out cells have shown that NDUFB7 is one of the subunits strictly required for assembly of a functional mitochondrial complex I subunit, which is essential for cell viability (PMID 27626371).
Inborn errors of metabolism v2.122 NDUFB7 Sarah Leigh Gene: ndufb7 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorder with complex I deficiency v1.12 NDUFB7 Sarah Leigh Tag watchlist tag was added to gene: NDUFB7.
Inborn errors of metabolism v2.121 NDUFB7 Sarah Leigh Publications for gene: NDUFB7 were set to 33502047; 27626371
Mitochondrial disorders v2.30 NDUFB7 Sarah Leigh Tag watchlist tag was added to gene: NDUFB7.
Inborn errors of metabolism v2.121 NDUFB7 Sarah Leigh Publications for gene: NDUFB7 were set to
Mitochondrial disorder with complex I deficiency v1.12 NDUFB7 Sarah Leigh Publications for gene: NDUFB7 were set to
Mitochondrial disorders v2.30 NDUFB7 Sarah Leigh Mode of inheritance for gene: NDUFB7 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorder with complex I deficiency v1.11 NDUFB7 Sarah Leigh Mode of inheritance for gene: NDUFB7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorder with complex I deficiency v1.10 NDUFB7 Sarah Leigh Classified gene: NDUFB7 as Amber List (moderate evidence)
Mitochondrial disorder with complex I deficiency v1.10 NDUFB7 Sarah Leigh Added comment: Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one biallelic splicing variant reported. RNA sequencing revealed that this variant disrupted normal splicing (PMID 33502047) and human knock-out cells have shown that NDUFB7 is one of the subunits strictly required for assembly of a functional mitochondrial complex I subunit, which is essential for cell viability (PMID 27626371).
Mitochondrial disorder with complex I deficiency v1.10 NDUFB7 Sarah Leigh Gene: ndufb7 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.29 NDUFB7 Sarah Leigh Classified gene: NDUFB7 as Amber List (moderate evidence)
Mitochondrial disorders v2.29 NDUFB7 Sarah Leigh Added comment: Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one biallelic splicing variant reported. RNA sequencing revealed that this variant disrupted normal splicing (PMID 33502047) and human knock-out cells have shown that NDUFB7 is one of the subunits strictly required for assembly of a functional mitochondrial complex I subunit, which is essential for cell viability (PMID 27626371).
Mitochondrial disorders v2.29 NDUFB7 Sarah Leigh Gene: ndufb7 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.28 NDUFB7 Sarah Leigh Publications for gene: NDUFB7 were set to
Clefting v2.28 ACBD5 Arina Puzriakova Classified gene: ACBD5 as Red List (low evidence)
Clefting v2.28 ACBD5 Arina Puzriakova Added comment: Comment on list classification: Only a single patient reported with a cleft palate to date, and therefore rating Red on this panel.
Clefting v2.28 ACBD5 Arina Puzriakova Gene: acbd5 has been classified as Red List (Low Evidence).
Clefting v2.27 ACBD5 Arina Puzriakova Phenotypes for gene: ACBD5 were changed from Cleft palate to Retinal dystrophy with leukodystrophy, OMIM:618863
Clefting v2.26 ACBD5 Arina Puzriakova Publications for gene: ACBD5 were set to
Clefting v2.25 ACBD5 Arina Puzriakova Mode of inheritance for gene: ACBD5 was changed from to BIALLELIC, autosomal or pseudoautosomal
Inherited white matter disorders v1.90 ACBD5 Arina Puzriakova Publications for gene: ACBD5 were set to 27799409, 27899449, 23105016
Inherited white matter disorders v1.89 ACBD5 Arina Puzriakova Phenotypes for gene: ACBD5 were changed from to Retinal dystrophy with leukodystrophy, OMIM:618863
Inherited white matter disorders v1.88 ACBD5 Arina Puzriakova Classified gene: ACBD5 as Green List (high evidence)
Inherited white matter disorders v1.88 ACBD5 Arina Puzriakova Gene: acbd5 has been classified as Green List (High Evidence).
Inherited white matter disorders v1.87 ACBD5 Arina Puzriakova reviewed gene: ACBD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23105016, 27899449, 27799409, 33427402; Phenotypes: Retinal dystrophy with leukodystrophy, OMIM:618863; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.44 ACBD5 Arina Puzriakova Phenotypes for gene: ACBD5 were changed from Retinal dystrophy with leukodystrophy, OMIM:618863 to Retinal dystrophy with leukodystrophy, OMIM:618863
White matter disorders and cerebral calcification - narrow panel v1.43 ACBD5 Arina Puzriakova Publications for gene: ACBD5 were set to 23105016; 27899449; 27799409; 33427402
Peroxisomal disorders v1.12 ACBD5 Arina Puzriakova Publications for gene: ACBD5 were set to 27799409; 23105016; 33427402
White matter disorders and cerebral calcification - narrow panel v1.42 ACBD5 Arina Puzriakova Publications for gene: ACBD5 were set to 27799409, 27899449, 23105016
White matter disorders and cerebral calcification - narrow panel v1.41 ACBD5 Arina Puzriakova Phenotypes for gene: ACBD5 were changed from to Retinal dystrophy with leukodystrophy, OMIM:618863
White matter disorders and cerebral calcification - narrow panel v1.40 ACBD5 Arina Puzriakova Classified gene: ACBD5 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.40 ACBD5 Arina Puzriakova Added comment: Comment on list classification: There is are sufficient unrelated cases (3) to support a diagnostic-grade classification (Green) at the next GMS panel update
White matter disorders and cerebral calcification - narrow panel v1.40 ACBD5 Arina Puzriakova Gene: acbd5 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v1.39 ACBD5 Arina Puzriakova Tag Q2_21_rating tag was added to gene: ACBD5.
White matter disorders and cerebral calcification - narrow panel v1.39 ACBD5 Arina Puzriakova reviewed gene: ACBD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23105016, 27799409, 33427402; Phenotypes: Retinal dystrophy with leukodystrophy, OMIM:618863; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Peroxisomal disorders v1.11 ACBD5 Arina Puzriakova Tag Q2_21_rating was removed from gene: ACBD5.
Peroxisomal disorders v1.11 ACBD5 Arina Puzriakova changed review comment from: Comment on list classification: There is are sufficient unrelated cases (4) to promote this gene to Green at the next GMS panel update.; to: Comment on list classification: There is are sufficient unrelated cases (4) to support a diagnostic-grade classification (Green)
Peroxisomal disorders v1.11 ACBD5 Arina Puzriakova Classified gene: ACBD5 as Green List (high evidence)
Peroxisomal disorders v1.11 ACBD5 Arina Puzriakova Gene: acbd5 has been classified as Green List (High Evidence).
Peroxisomal disorders v1.10 ACBD5 Arina Puzriakova Phenotypes for gene: ACBD5 were changed from Retinal dystrophy with leukodystrophy (MIM#618863) to Retinal dystrophy with leukodystrophy, OMIM:618863
Peroxisomal disorders v1.9 ACBD5 Arina Puzriakova Publications for gene: ACBD5 were set to 27799409; 23105016
Peroxisomal disorders v1.8 ACBD5 Arina Puzriakova Classified gene: ACBD5 as Amber List (moderate evidence)
Peroxisomal disorders v1.8 ACBD5 Arina Puzriakova Added comment: Comment on list classification: There is are sufficient unrelated cases (4) to promote this gene to Green at the next GMS panel update.
Peroxisomal disorders v1.8 ACBD5 Arina Puzriakova Gene: acbd5 has been classified as Amber List (Moderate Evidence).
Peroxisomal disorders v1.7 ACBD5 Arina Puzriakova Tag Q2_21_rating tag was added to gene: ACBD5.
Peroxisomal disorders v1.7 ACBD5 Arina Puzriakova commented on gene: ACBD5: A fourth individual was identified by Dr Helen Brittain (Genomics England Clinical Fellow) who presented with retinal dystrophy, ataxia and developmental regression at 2 yrs old
Peroxisomal disorders v1.7 ACBD5 Arina Puzriakova reviewed gene: ACBD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 33427402; Phenotypes: Retinal dystrophy with leukodystrophy, OMIM:618863; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v2.184 ACBD5 Arina Puzriakova Publications for gene: ACBD5 were set to 27799409; 23105016
Retinal disorders v2.183 ACBD5 Arina Puzriakova Classified gene: ACBD5 as Amber List (moderate evidence)
Retinal disorders v2.183 ACBD5 Arina Puzriakova Added comment: Comment on list classification: There is are now sufficient unrelated cases (4) of retinal dystrophy in patients with biallelic ACBD5 variants to promote this gene to Green at the next GMS panel update.
Retinal disorders v2.183 ACBD5 Arina Puzriakova Gene: acbd5 has been classified as Amber List (Moderate Evidence).
Retinal disorders v2.182 ACBD5 Arina Puzriakova Tag watchlist was removed from gene: ACBD5.
Tag Q2_21_rating tag was added to gene: ACBD5.
Retinal disorders v2.182 ACBD5 Arina Puzriakova commented on gene: ACBD5: A fourth individual was identified by Dr Helen Brittain (Genomics England Clinical Fellow) who presented with retinal dystrophy, ataxia and developmental regression at 2 yrs old
Retinal disorders v2.182 ACBD5 Arina Puzriakova reviewed gene: ACBD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 33427402; Phenotypes: Retinal dystrophy with leukodystrophy, OMIM:618863; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inborn errors of metabolism v2.120 NDUFA12 Sarah Leigh Phenotypes for gene: NDUFA12 were changed from ?Mitochondrial complex I deficiency, nuclear type 23 OMIM:618244; mitochondrial complex 1 deficiency, nuclear type 23 MONDO:0032627 to ?Mitochondrial complex I deficiency, nuclear type 23 OMIM:618244; mitochondrial complex 1 deficiency, nuclear type 23 MONDO:0032627
Inborn errors of metabolism v2.119 NDUFA12 Sarah Leigh Publications for gene: NDUFA12 were set to 21617257; 27604308; 33715266
Inborn errors of metabolism v2.119 NDUFA12 Sarah Leigh Publications for gene: NDUFA12 were set to 21617257; 27604308; 33715266
Inborn errors of metabolism v2.118 NDUFA12 Sarah Leigh Publications for gene: NDUFA12 were set to 21617257; 27604308; 33715266
Inborn errors of metabolism v2.118 NDUFA12 Sarah Leigh Publications for gene: NDUFA12 were set to 21617257; 27604308; 33715266
Inborn errors of metabolism v2.117 NDUFA12 Sarah Leigh Phenotypes for gene: NDUFA12 were changed from ?Mitochondrial complex I deficiency, nuclear type 23 618244 to ?Mitochondrial complex I deficiency, nuclear type 23 OMIM:618244; mitochondrial complex 1 deficiency, nuclear type 23 MONDO:0032627
Inborn errors of metabolism v2.117 NDUFA12 Sarah Leigh Publications for gene: NDUFA12 were set to 21617257; 27604308
Inborn errors of metabolism v2.116 NDUFA12 Sarah Leigh edited their review of gene: NDUFA12: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least five variants reported in five unrelated cases, together with supportive studies. Phenotypic variability was evident in the cases reported (PMID: 21617257; 33715266).; Changed rating: GREEN
Inborn errors of metabolism v2.116 NDUFA12 Sarah Leigh Tag Q2_21_rating tag was added to gene: NDUFA12.
Inborn errors of metabolism v2.116 NDUFA12 Sarah Leigh Classified gene: NDUFA12 as Amber List (moderate evidence)
Inborn errors of metabolism v2.116 NDUFA12 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Inborn errors of metabolism v2.116 NDUFA12 Sarah Leigh Gene: ndufa12 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.27 NDUFA12 Sarah Leigh edited their review of gene: NDUFA12: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least five variants reported in five unrelated cases, together with supportive studies. Phenotypic variability was evident in the cases reported (PMID: 21617257; 33715266).; Changed rating: GREEN
Mitochondrial disorders v2.27 NDUFA12 Sarah Leigh Classified gene: NDUFA12 as Amber List (moderate evidence)
Mitochondrial disorders v2.27 NDUFA12 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v2.27 NDUFA12 Sarah Leigh Gene: ndufa12 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.26 NDUFA12 Sarah Leigh Tag Q2_21_rating tag was added to gene: NDUFA12.
Primary immunodeficiency v2.413 SASH3 Boaz Palterer gene: SASH3 was added
gene: SASH3 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: SASH3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SASH3 were set to Combined immunodeficiency; lymphopenia; neutropenia; immunodysregulation; autoimmune cytopenias
Penetrance for gene: SASH3 were set to unknown
Review for gene: SASH3 was set to GREEN
Added comment: Delmonte et al. described three novel SASH3 deleterious variants in four unrelated male patients with a history of combined immunodeficiency and immune dysregulation manifesting as recurrent sinopulmonary, cutaneous and mucosal infections, and refractory autoimmune cytopenias.
Functional data: Lentivirus-mediated transfer of SASH3 cDNA in KO Jurkat cells and patient's cell lines restored protein expression and cell proliferation. The KO mouse phenotype is compatible.
https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2020008629/475781/SASH3-variants-cause-a-novel-form-of-X-linked?redirectedFrom=fulltext
Sources: Literature
Intellectual disability v3.1033 NCKAP1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: NCKAP1.
Intellectual disability v3.1033 NCKAP1 Arina Puzriakova Classified gene: NCKAP1 as Amber List (moderate evidence)
Intellectual disability v3.1033 NCKAP1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. Guo et al 2020 (PMID:33157009) describe multiple families with inherited and de novo deleterious NCKAP1 variants. Neurodevelopmental features represent the core phenotypes, including autistic features, psychomotor delays, and ID or learning disabilities (10/16 individuals had a diagnosis of mild to severe ID)
Intellectual disability v3.1033 NCKAP1 Arina Puzriakova Gene: nckap1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1032 NCKAP1 Arina Puzriakova Phenotypes for gene: NCKAP1 were changed from to Intellectual disability; Autism
Intellectual disability v3.1031 NCKAP1 Arina Puzriakova Publications for gene: NCKAP1 were set to
Intellectual disability v3.1030 NCKAP1 Arina Puzriakova Mode of inheritance for gene: NCKAP1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.1029 DPYS Arina Puzriakova Tag Q2_21_expert_review tag was added to gene: DPYS.
Intellectual disability v3.1029 DPYS Arina Puzriakova Publications for gene: DPYS were set to
Intellectual disability v3.1028 DPYS Arina Puzriakova Classified gene: DPYS as Amber List (moderate evidence)
Intellectual disability v3.1028 DPYS Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Overall variable clinical presentation, even including asymptomatic subjects. However, DD and/or ID have been reported in multiple published cases (PMIDs: 9266350; 17383919; 20362666; 27604308; 26771602; 29054612). Sufficient unrelated cases (>3) to rate Green but will seek opinion from the GMS expert group due to highly variable penetrance of this phenotype.
Intellectual disability v3.1028 DPYS Arina Puzriakova Gene: dpys has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.26 NDUFA12 Sarah Leigh Added comment: Comment on phenotypes: Isolated complex I deficiency;
Mitochondrial disorders v2.26 NDUFA12 Sarah Leigh Phenotypes for gene: NDUFA12 were changed from Isolated complex I deficiency; ?Mitochondrial complex I deficiency, nuclear type 23, 618244 to ?Mitochondrial complex I deficiency, nuclear type 23 OMIM:618244; mitochondrial complex 1 deficiency, nuclear type 23 MONDO:0032627
Mitochondrial disorders v2.25 NDUFA12 Sarah Leigh Publications for gene: NDUFA12 were set to 21617257
White matter disorders and cerebral calcification - narrow panel v1.39 CLDN11 Sarah Leigh changed review comment from: Not associated with relevant phenotype in OMIM (entry last edited on 01/14/2013) or Gen2Phen. Two stop loss variants reported in three unrelated cases. Both variants resulted in an 39aa extension - c.622T>C, p.(208Glnext*39) in two individuals and c.622T>G, p.(*208Gluext*39) in one individual, all occurring de novo. At the RNA level, the variant c.622T>C did not lead to a loss of expression in fibroblasts, indicating this transcript is not subject to nonsense-mediated decay (PMID 33313762). The reporting authors predict that the extended claudin-11 forms an alpha helix which is not incorporated into the cytoplasmic membrane, possibly perturbing its interaction with intracellular proteins.; to: Not associated with relevant phenotype in OMIM (entry last edited on 01/14/2013) or Gen2Phen. Two stop loss variants reported in three unrelated cases. Both variants resulted in an 39aa extension - c.622T>C, p.(208Glnext*39) in two individuals and c.622T>G, p.(208Gluext*39) in one individual, all occurring de novo. At the RNA level, the variant c.622T>C did not lead to a loss of expression in fibroblasts, indicating this transcript is not subject to nonsense-mediated decay (PMID 33313762). The reporting authors predict that the extended claudin-11 forms an alpha helix which is not incorporated into the cytoplasmic membrane, possibly perturbing its interaction with intracellular proteins.
White matter disorders and cerebral calcification - narrow panel v1.39 CLDN11 Sarah Leigh edited their review of gene: CLDN11: Added comment: Not associated with relevant phenotype in OMIM (entry last edited on 01/14/2013) or Gen2Phen. Two stop loss variants reported in three unrelated cases. Both variants resulted in an 39aa extension - c.622T>C, p.(208Glnext*39) in two individuals and c.622T>G, p.(*208Gluext*39) in one individual, all occurring de novo. At the RNA level, the variant c.622T>C did not lead to a loss of expression in fibroblasts, indicating this transcript is not subject to nonsense-mediated decay (PMID 33313762). The reporting authors predict that the extended claudin-11 forms an alpha helix which is not incorporated into the cytoplasmic membrane, possibly perturbing its interaction with intracellular proteins.; Changed rating: GREEN
White matter disorders and cerebral calcification - narrow panel v1.39 CLDN11 Sarah Leigh Tag Q2_21_rating tag was added to gene: CLDN11.
White matter disorders and cerebral calcification - narrow panel v1.39 CLDN11 Sarah Leigh Classified gene: CLDN11 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.39 CLDN11 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
White matter disorders and cerebral calcification - narrow panel v1.39 CLDN11 Sarah Leigh Gene: cldn11 has been classified as Amber List (Moderate Evidence).
Retinal disorders v2.182 FAM57B Ivone Leong Phenotypes for gene: FAM57B were changed from Cone-rod dystrophy to Cone-rod dystrophy, MONDO:0015993; Maculopathy
Retinal disorders v2.181 FAM57B Ivone Leong Publications for gene: FAM57B were set to 28041643
Retinal disorders v2.180 FAM57B Ivone Leong Mode of inheritance for gene: FAM57B was changed from to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v2.179 CTNNA1 Ivone Leong Phenotypes for gene: CTNNA1 were changed from Macular dystrophy, patterned, 2, OMIM:608970 to Macular dystrophy, patterned, 2, OMIM:608970; exudative vitreoretinopathy, MONDO:0019516
Retinal disorders v2.178 CTNNA1 Ivone Leong Publications for gene: CTNNA1 were set to 26691986
Inborn errors of metabolism v2.115 DPYS Arina Puzriakova Phenotypes for gene: DPYS were changed from Dihydropyrimidinase deficiency (Disorders of pyrimidine metabolism) to Dihydropyrimidinuria, OMIM:222748; Dihydropyrimidinase deficiency (Disorders of pyrimidine metabolism)
Intellectual disability v3.1027 DPYS Arina Puzriakova Phenotypes for gene: DPYS were changed from Dihydropyrimidinuria, MIM#222748 to Dihydropyrimidinuria, OMIM:222748
Undiagnosed metabolic disorders v1.454 DPYS Arina Puzriakova Phenotypes for gene: DPYS were changed from Dihydropyrimidinase deficiency (Disorders of pyrimidine metabolism) to Dihydropyrimidinuria, OMIM:222748; Dihydropyrimidinase deficiency (Disorders of pyrimidine metabolism)
Cardiomyopathies - including childhood onset v1.37 RHBDF1 Ivone Leong Tag watchlist tag was added to gene: RHBDF1.
Cardiomyopathies - including childhood onset v1.37 RHBDF1 Ivone Leong Classified gene: RHBDF1 as Amber List (moderate evidence)
Cardiomyopathies - including childhood onset v1.37 RHBDF1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Cardiomyopathies - including childhood onset v1.37 RHBDF1 Ivone Leong Gene: rhbdf1 has been classified as Amber List (Moderate Evidence).
Inborn errors of metabolism v2.114 DPM2 Arina Puzriakova Publications for gene: DPM2 were set to 23109149
Inborn errors of metabolism v2.113 DPM2 Arina Puzriakova Phenotypes for gene: DPM2 were changed from Congenital disorder of glycosylation, type Iu 615042; Congenital disorder of glycosylation, type Iu 615042 to Congenital disorder of glycosylation, type Iu, OMIM:615042
Cardiomyopathies - including childhood onset v1.36 RHBDF1 Ivone Leong Phenotypes for gene: RHBDF1 were changed from Dilated cardiomyopathy to Dilated cardiomyopathy, MONDO:0005021
Congenital muscular dystrophy v2.8 DPM2 Arina Puzriakova Phenotypes for gene: DPM2 were changed from musclular dystrophy dystroglycanopathy syndrome with severe epilepsy; Congenital disorder of glycosylation, type Iu 615042 to Congenital disorder of glycosylation, type Iu, OMIM:615042
Dilated cardiomyopathy - adult and teen v1.22 MYLK3 Ivone Leong Classified gene: MYLK3 as Amber List (moderate evidence)
Dilated cardiomyopathy - adult and teen v1.22 MYLK3 Ivone Leong Gene: mylk3 has been classified as Amber List (Moderate Evidence).
Dilated cardiomyopathy - adult and teen v1.21 MYLK3 Ivone Leong gene: MYLK3 was added
gene: MYLK3 was added to Dilated cardiomyopathy - adult and teen. Sources: Literature
Q2_21_rating tags were added to gene: MYLK3.
Mode of inheritance for gene: MYLK3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYLK3 were set to 29235529; 31244672; 32213617; 32870709; 30690923
Phenotypes for gene: MYLK3 were set to Dilated cardiomyopathy, MONDO:0005021
Review for gene: MYLK3 was set to GREEN
Added comment: This gene is also on the Cardiomyopathies - including childhood onset (Version 1.35) as an Amber gene with a recommendation of promoting to Green. This gene is not associated with a phenotype on OMIM or Gene2Phenotype.

PMID: 29235529 describes 2 families with heterozygous variant in this gene. Family A - 2 sibs diagnosed with DCM at 9 and 10 months of age and affected mother diagnosed with DCM at 40 yo. As the children had a more severe phenotype and earlier onset than the mother the authors did further analysis and found the sibs had an additional variant in FLNC, which is also linked to DCM. The authors suggest this additional variant could account for the more severe phenotype in the children.

Family B - 2 brothers diagnosed with DCM at 56 and 52 yo, both have a heterozygous frameshift variant in this gene. Mother and sister had died young and DCM diagnosis is inconclusive.

PMID: 30690923 describes another case. Proband has a heterozygous frameshift variant in this gene. Rest of the family have no cardiac phenotype and no variants in this gene except for one daughter. Daughter has the same variant and has dilation of LV and ST-T abnormalities but these do not meet the criteria for DCM.

PMID: 32870709 describes three consanguineous families with homozygous variants in this gene.

Review from Zornitza Stark:
"Rating: I don't know

Two families reported with mono-allelic variants (one extension, one frameshift), and three consanguineous families reported with bi-allelic variants (two hmz frameshift, one hmz missense). Supportive mouse models.
Sources: Literature
Created: 16 Apr 2021, 9:24 a.m."

There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Sources: Literature
Arthrogryposis v3.92 DPM2 Arina Puzriakova Phenotypes for gene: DPM2 were changed from congenital muscular dystrophies; congenital muscular dystrophies. DPM2-CDG . Musclular dystrophy dystroglycanopathy syndrome with severe epilepsy. to Congenital disorder of glycosylation, type Iu, OMIM:615042
Genetic epilepsy syndromes v2.324 DPM2 Arina Puzriakova Phenotypes for gene: DPM2 were changed from Congenital disorder of glycosylation, type Iu 615042; seizures to Congenital disorder of glycosylation, type Iu, OMIM:615042
Cardiomyopathies - including childhood onset v1.35 MYLK3 Ivone Leong Classified gene: MYLK3 as Amber List (moderate evidence)
Cardiomyopathies - including childhood onset v1.35 MYLK3 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype on OMIM or Gene2Phenotype.

PMID: 29235529 describes 2 families with heterozygous variant in this gene. Family A - 2 sibs diagnosed with DCM at 9 and 10 months of age and affected mother diagnosed with DCM at 40 yo. As the children had a more severe phenotype and earlier onset than the mother the authors did further analysis and found the sibs had an additional variant in FLNC, which is also linked to DCM. The authors suggest this additional variant could account for the more severe phenotype in the children.

Family B - 2 brothers diagnosed with DCM at 56 and 52 yo, both have a heterozygous frameshift variant in this gene. Mother and sister had died young and DCM diagnosis is inconclusive.

PMID: 30690923 describes another case. Proband has a heterozygous frameshift variant in this gene. Rest of the family have no cardiac phenotype and no variants in this gene except for one daughter. Daughter has the same variant and has dilation of LV and ST-T abnormalities but these do not meet the criteria for DCM.

PMID: 32870709 describes three consanguineous families with homozygous variants in this gene.

There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Cardiomyopathies - including childhood onset v1.35 MYLK3 Ivone Leong Gene: mylk3 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v2.323 DPM2 Arina Puzriakova commented on gene: DPM2
Congenital disorders of glycosylation v2.70 DPM2 Arina Puzriakova Phenotypes for gene: DPM2 were changed from Congenital disorder of glycosylation, type Iu 615042 to Congenital disorder of glycosylation, type Iu, OMIM:615042
Congenital disorders of glycosylation v2.69 DPM2 Arina Puzriakova Publications for gene: DPM2 were set to 23109149
Congenital disorders of glycosylation v2.68 DPM2 Arina Puzriakova Classified gene: DPM2 as Amber List (moderate evidence)
Congenital disorders of glycosylation v2.68 DPM2 Arina Puzriakova Added comment: Comment on list classification: Associated with relevant phenotype in OMIM (MIM# 615042). Sufficient number of unrelated cases (3) with DPM2-CDG to rate Green at the next GMS panel update (PMIDs: 23109149; 33129689)
Congenital disorders of glycosylation v2.68 DPM2 Arina Puzriakova Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Cardiomyopathies - including childhood onset v1.34 MYLK3 Ivone Leong Publications for gene: MYLK3 were set to 29235529; 31244672; 32213617; 32870709
Cardiomyopathies - including childhood onset v1.33 MYLK3 Ivone Leong Tag Q2_21_rating tag was added to gene: MYLK3.
Cardiomyopathies - including childhood onset v1.33 MYLK3 Ivone Leong Phenotypes for gene: MYLK3 were changed from Dilated cardiomyopathy to Dilated cardiomyopathy, MONDO:0005021
Congenital disorders of glycosylation v2.67 DPM2 Arina Puzriakova Tag Q2_21_rating tag was added to gene: DPM2.
Intellectual disability v3.1026 DPM2 Arina Puzriakova Tag Q2_21_rating tag was added to gene: DPM2.
Intellectual disability v3.1026 DPM2 Arina Puzriakova Publications for gene: DPM2 were set to 23109149
Intellectual disability v3.1025 DPM2 Arina Puzriakova Classified gene: DPM2 as Amber List (moderate evidence)
Intellectual disability v3.1025 DPM2 Arina Puzriakova Added comment: Comment on list classification: Associated with relevant phenotype in OMIM (MIM# 615042). Sufficient number of unrelated cases (3) with DPM2-CDG to rate Green at the next GMS panel update. Phenotypes include intellectual disability in all affected individuals.
Intellectual disability v3.1025 DPM2 Arina Puzriakova Gene: dpm2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1024 DPM2 Arina Puzriakova Phenotypes for gene: DPM2 were changed from Congenital disorder of glycosylation, type Iu to Congenital disorder of glycosylation, type Iu, OMIM:615042
Cardiomyopathies - including childhood onset v1.32 MCM10 Ivone Leong Classified gene: MCM10 as Red List (low evidence)
Cardiomyopathies - including childhood onset v1.32 MCM10 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with any phenotypes in OMIM or Gene2Phenotype. Currently, there is not enough evidence to support a gene-disease association. Therefore this gene has been given a Red rating.
Cardiomyopathies - including childhood onset v1.32 MCM10 Ivone Leong Gene: mcm10 has been classified as Red List (Low Evidence).
Cardiomyopathies - including childhood onset v1.31 MCM10 Ivone Leong Phenotypes for gene: MCM10 were changed from Restrictive cardiomyopathy to Restrictive cardiomyopathy, MONDO:0005201
Dilated cardiomyopathy - adult and teen v1.20 NRAP Ivone Leong Publications for gene: NRAP were set to 30384889; 33534821; 28611399; https://doi.org/10.1101/2020.10.12.20211474
Primary immunodeficiency v2.413 ZNFX1 Boaz Palterer edited their review of gene: ZNFX1: Added comment: Multisystem Inflammation and Susceptibility to Viral infections in Human ZNFX1 Deficiency
15 patients from 8 families with an autosomal recessive immunodeficiency characterized by severe infections by both RNA and DNA viruses and virally triggered inflammatory episodes with hemophagocytic-lymphohistiocytosis-like disease, early-onset seizures, as well as renal and lung disease.
https://www.jacionline.org/article/S0091-6749(21)00613-8/fulltext; Changed rating: GREEN; Changed phenotypes: Multisystem inflammatory disoder, viral infections, HLH
Inborn errors of metabolism v2.112 B4GALT1 Arina Puzriakova Phenotypes for gene: B4GALT1 were changed from Beta-1,4-galactosyltransferase 1 deficiency (Disorders of multiple glycosylation and other glycosylation pathways); Congenital disorder of glycosylation, type IId 607091 to Congenital disorder of glycosylation, type IId, OMIM:607091
Undiagnosed metabolic disorders v1.453 B4GALT1 Arina Puzriakova Phenotypes for gene: B4GALT1 were changed from Beta-1,4-galactosyltransferase 1 deficiency (Disorders of multiple glycosylation and other glycosylation pathways); Congenital disorder of glycosylation, type IId 607091; Beta-1,4-galactosyltransferase 1 deficiency (Disorders of multiple glycosylation and other glycosylation pathways) to Congenital disorder of glycosylation, type IId, OMIM:607091
Congenital disorders of glycosylation v2.67 B4GALT1 Arina Puzriakova Phenotypes for gene: B4GALT1 were changed from Congenital disorder of glycosylation, type IId 607091; Beta-1,4-galactosyltransferase 1 deficiency (Disorders of multiple glycosylation and other glycosylation pathways) to Congenital disorder of glycosylation, type IId, OMIM:607091
Intellectual disability v3.1023 B4GALT1 Arina Puzriakova Publications for gene: B4GALT1 were set to 26503795; 24896178; 11901181; 21920538; 30653653
Intellectual disability v3.1022 B4GALT1 Arina Puzriakova Classified gene: B4GALT1 as Amber List (moderate evidence)
Intellectual disability v3.1022 B4GALT1 Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber as now there are 2 families (4 total) exhibiting severe cognitive impairment, albeit this resolved in the singleton by age 11 (remaining patients were age 2.5, 11 and 11 years at the time of reporting)
Intellectual disability v3.1022 B4GALT1 Arina Puzriakova Gene: b4galt1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.1021 B4GALT1 Arina Puzriakova reviewed gene: B4GALT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 11901181, 21920538, 30653653, 32157688; Phenotypes: Congenital disorder of glycosylation, type IId, OMIM:607091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.123 TDP2 Ivone Leong Phenotypes for gene: TDP2 were changed from Spinocerebellar ataxia, autosomal recessive 23, 616949 to Spinocerebellar ataxia, autosomal recessive 23, OMIM:616949
Structural eye disease v1.66 TBC1D23 Ivone Leong gene: TBC1D23 was added
gene: TBC1D23 was added to Structural eye disease. Sources: Literature
Mode of inheritance for gene: TBC1D23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D23 were set to 28823707; 28823706; 32360255
Phenotypes for gene: TBC1D23 were set to coloboma, MONDO:0001476; strabismus, MONDO:0003432
Review for gene: TBC1D23 was set to RED
Added comment: PMID:28823707. 2 of 3 unrelated families (4 of 7 affected individuals) had ataxia. 1 family (3 affected individuals) had coloboma and strabismus. 1 family (1 individual) had hyperopia and strabismus.

PMID:28823706. 2 of 4 unrelated families (4 of 6 affected individuals) had ataxia. 2 of 6 individuals with eye phenotype (strabismus or esotropia of the left eye). Zebrafish morpholino knockout model showed reduced eye size.

PMID: 32360255. 1 case with ataxia. No eye phenotype reported.

Despite there being a zebrafish model with an eye phenotype, there is only 1 family out of 8 who had coloboma, therefore this gene is given a Red rating until more evidence is available.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.122 TBC1D23 Ivone Leong Phenotypes for gene: TBC1D23 were changed from Pontocerebellar hypoplasia, type 11, MIM# 617695 to Pontocerebellar hypoplasia, type 11, OMIM:617695
Ataxia and cerebellar anomalies - narrow panel v2.121 TBC1D23 Ivone Leong Classified gene: TBC1D23 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.121 TBC1D23 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Ataxia and cerebellar anomalies - narrow panel v2.121 TBC1D23 Ivone Leong Gene: tbc1d23 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.120 TBC1D23 Ivone Leong Tag Q2_21_rating tag was added to gene: TBC1D23.
Ataxia and cerebellar anomalies - narrow panel v2.120 TBC1D23 Ivone Leong Added comment: Comment on publications: PMID:28823707. 2 of 3 unrelated families (4 of 7 affected individuals) had ataxia. 1 family (3 affected individuals) had coloboma and strabismus. 1 family (1 individual) had hyperopia and strabismus.

PMID:28823706. 2 of 4 unrelated families (4 of 6 affected individuals) had ataxia. 2 of 6 individuals with eye phenotype (strabismus or esotropia of the left eye).

PMID: 32360255. 1 case with ataxia. No eye phenotype reported.
Ataxia and cerebellar anomalies - narrow panel v2.120 TBC1D23 Ivone Leong Publications for gene: TBC1D23 were set to 28823707; 28823706
Intellectual disability v3.1021 B4GALT1 Arina Puzriakova Publications for gene: B4GALT1 were set to 26503795; 24896178; 11901181; 21920538
Intellectual disability v3.1020 B4GALT1 Arina Puzriakova Phenotypes for gene: B4GALT1 were changed from Congenital disorder of glycosylation, type IId 607091 to Congenital disorder of glycosylation, type IId, OMIM:607091
Intellectual disability v3.1019 AGO1 Arina Puzriakova Tag Q2_21_expert_review tag was added to gene: AGO1.
Intellectual disability v3.1019 AGO1 Arina Puzriakova commented on gene: AGO1
Intellectual disability v3.1019 AGO1 Arina Puzriakova Publications for gene: AGO1 were set to 26350204; 30213762; 22495306; 23020937; 25363768; 25356899; 27620904; 29346770
Ataxia and cerebellar anomalies - narrow panel v2.119 SQSTM1 Ivone Leong Classified gene: SQSTM1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.119 SQSTM1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Ataxia and cerebellar anomalies - narrow panel v2.119 SQSTM1 Ivone Leong Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.118 SQSTM1 Ivone Leong Tag Q2_21_rating tag was added to gene: SQSTM1.
Ataxia and cerebellar anomalies - narrow panel v2.118 SQSTM1 Ivone Leong Publications for gene: SQSTM1 were set to 27545679
Ataxia and cerebellar anomalies - narrow panel v2.117 SQSTM1 Ivone Leong Phenotypes for gene: SQSTM1 were changed from Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, MIM# 617145 to Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, OMIM:617145
Ataxia and cerebellar anomalies - narrow panel v2.116 SPR Ivone Leong Classified gene: SPR as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.116 SPR Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Ataxia and cerebellar anomalies - narrow panel v2.116 SPR Ivone Leong Gene: spr has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.115 SPR Ivone Leong Tag Q2_21_rating tag was added to gene: SPR.
Ataxia and cerebellar anomalies - narrow panel v2.115 SPR Ivone Leong Phenotypes for gene: SPR were changed from Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM# 612716 to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716
Ataxia and cerebellar anomalies - narrow panel v2.114 SPG7 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Spastic paraplegia 7 (#607259) complex forms of the disease. Actually associated with a range of phenotypes including adult-onset ataxia
Ataxia and cerebellar anomalies - narrow panel v2.114 SPG7 Ivone Leong Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7 (#607259) complex forms of the disease. Actually associated with a range of phenotypes including adult-onset ataxia to Spastic paraplegia 7, autosomal recessive, OMIM:607259
Ataxia and cerebellar anomalies - narrow panel v2.113 SPG7 Ivone Leong Publications for gene: SPG7 were set to PMID: 25681447
Ataxia and cerebellar anomalies - narrow panel v2.112 SNAP25 Ivone Leong Classified gene: SNAP25 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.112 SNAP25 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Ataxia and cerebellar anomalies - narrow panel v2.112 SNAP25 Ivone Leong Gene: snap25 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.111 SNAP25 Ivone Leong Tag Q2_21_rating tag was added to gene: SNAP25.
Ataxia and cerebellar anomalies - narrow panel v2.111 SNAP25 Ivone Leong Phenotypes for gene: SNAP25 were changed from Myasthenic syndrome, congenital, 18, 616330; cerebellar ataxia and seizures to ?Myasthenic syndrome, congenital, 18, OMIM:616330; cerebellar ataxia, MONDO:0000437; seizures, HP:0001250
Skeletal ciliopathies v1.10 PDIA6 Zornitza Stark gene: PDIA6 was added
gene: PDIA6 was added to Skeletal ciliopathies. Sources: Literature
Mode of inheritance for gene: PDIA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDIA6 were set to 33495992
Phenotypes for gene: PDIA6 were set to Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes
Review for gene: PDIA6 was set to AMBER
Added comment: 1 case with asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes. Whole exome sequencing revealed a homozygous frameshift variant in the PDIA6 gene. RNA expression was reduced in a gene dosage‐dependent manner, supporting a loss‐of‐function effect of this variant. Phenotypic correlation with the previously reported mouse model recapitulated the growth defect and delay, early lethality, coagulation, diabetes, immunological, and polycystic kidney disease phenotypes. The phenotype of the current patient is consistent with phenotypes associated with the disruption of PDIA6 and the sensors of UPR in mice and humans.

Rated Amber in view of the high impact variant combined with functional data including a mouse model.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.110 EXOSC1 Zornitza Stark gene: EXOSC1 was added
gene: EXOSC1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: EXOSC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC1 were set to 33463720
Phenotypes for gene: EXOSC1 were set to Pontocerebellar hypoplasia
Review for gene: EXOSC1 was set to RED
Added comment: An 8‐months‐old male with developmental delay, microcephaly, subtle dysmorphism, hypotonia, pontocerebellar hypoplasia and delayed myelination. Similarly affected elder sibling succumbed at the age of 4‐years 6‐months. Exome sequencing revealed a homozygous missense variant (c.104C >T, p.Ser35Leu) in EXOSC1. In silico mutagenesis revealed loss of a polar contact with neighbouring Leu37 residue. Quantitative real‐time PCR indicated no appreciable differences in EXOSC1 transcript levels. Immunoblotting and blue native PAGE revealed reduction in the EXOSC1 protein levels and EXO9 complex in the proband, respectively. Of note, bi‐allelic variants in other exosome subunits EXOSC3, EXOSC8 and EXOSC9 have been reported to cause pontocerebellar hypoplasia type 1B, type 1C and type 1D, respectively.
Sources: Literature
Clefting v2.24 MED12 Zornitza Stark reviewed gene: MED12: Rating: GREEN; Mode of pathogenicity: None; Publications: 33244166; Phenotypes: Hardikar syndrome, OMIM #612726; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v3.1018 UBE4A Zornitza Stark gene: UBE4A was added
gene: UBE4A was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: UBE4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE4A were set to 33420346
Phenotypes for gene: UBE4A were set to Intellectual disability
Review for gene: UBE4A was set to GREEN
gene: UBE4A was marked as current diagnostic
Added comment: 8 individuals, from 4 unrelated families, with syndromic intellectual disability and global developmental delay (other clinical features included hypotonia, short stature, seizures, and behaviour disorder. Exome sequencing identified biallelic loss-of-function variants in UBE4A in the 4 families, with variants segregating with disease and parents carriers. They demonstrated that UBE4A loss-of-function variants reduced RNA expression and protein levels in clinical samples. Mice generated to mimic patient-specific Ube4a loss-of-function variant exhibited muscular and neurological/behavioural abnormalities, some of which are suggestive of the clinical abnormalities seen in the affected individuals.
Sources: Literature
Intellectual disability v3.1018 MAPKAPK5 Zornitza Stark gene: MAPKAPK5 was added
gene: MAPKAPK5 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: MAPKAPK5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAPKAPK5 were set to 3344202
Phenotypes for gene: MAPKAPK5 were set to Developmental delay, variable brain anomalies, congenital heart defects, dysmorphism
Review for gene: MAPKAPK5 was set to GREEN
gene: MAPKAPK5 was marked as current diagnostic
Added comment: 3 individuals from 2 families with severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with an additional hypoplastic digit between the fourth and fifth digits of hands and/or feet. Exome sequencing identified different homozygous truncating variants in MAPKAPK5 in both families, segregating with disease and unaffected parents as carriers.

Patient-derived cells showed no expression of MAPKAPK5 protein isoforms and reduced levels of the MAPKAPK5-interacting protein ERK3. F-actin recovery after latrunculin B treatment was found to be less efficient in patient-derived fibroblasts than in control cells, supporting a role of MAPKAPK5 in F-actin polymerization.

Borderline Amber/Green but high impact variants and a distinctive phenotype with some functional data.
Sources: Literature
Intellectual disability v3.1018 FAR1 Zornitza Stark edited their review of gene: FAR1: Added comment: PMID 33239752: 12 patients with paediatric onset spastic paraparesis and bilateral congenital/juvenile cataracts. Most also had speech and gross motor developmental delay and truncal hypotonia. Exome sequencing identified de novo variants affecting the Arg480 residue in FAR1 (p.Arg480Cys/His/Leu). Further functional studies in fibroblasts showed that these variants cause a disruption of the plasmalogen-dependent feedback regulation of FAR1 protein levels leading to uncontrolled ether lipid production.; Changed rating: GREEN; Changed publications: 25439727, 33239752; Changed phenotypes: Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154, spastic paraparesis and bilateral cataracts; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Distal myopathies v1.29 GIPC1 Zornitza Stark edited their review of gene: GIPC1: Added comment: PMID 33374016: a Chinese cohort of 41 patients with the clinical diagnosis of oculopharyngodistal myopathy (21 cases from seven families and 20 sporadic cases). Overall, the repeat expansion in GIPC1 was identified in 51.9% independent pedigrees (4/7 families and 10/20 sporadic cases). The number of CGG repeats was <30 in controls but >60 in affected individuals. There was a slight correlation between repeat size and the age at onset. Both repeat expansion and retraction were observed during transmission but somatic instability was not evident.; Changed publications: 32413282, 33374016
Retinal disorders v2.177 CTNNA1 Zornitza Stark edited their review of gene: CTNNA1: Added comment: In addition, three independent families reported with familial exudative vitreoretinopathy (FEVR) in PMID33497368.; Changed publications: 26691986, 33497368; Changed phenotypes: Macular dystrophy, butterfly-shaped pigmentary, 2, MIM# 608970, Familial exudative vitreoretinopathy
Arthrogryposis v3.91 ERBB3 Zornitza Stark reviewed gene: ERBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33720042; Phenotypes: Hirschsprung disease, arthrogryposis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v1.38 CLDN11 Zornitza Stark gene: CLDN11 was added
gene: CLDN11 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: CLDN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN11 were set to 33313762
Phenotypes for gene: CLDN11 were set to Hypomyelinating leukodystrophy
Review for gene: CLDN11 was set to GREEN
gene: CLDN11 was marked as current diagnostic
Added comment: In three unrelated individuals with early-onset spastic movement disorder, expressive speech disorder and eye abnormalities including hypermetropia, 2 different heterozygous de novo stop-loss variants were identified. One of the variants did not lead to a loss of CLDN11 expression on RNA level in fibroblasts indicating this transcript is not subject to nonsense-mediated decay and most likely translated into an extended protein.
Sources: Literature
Primary immunodeficiency v2.413 SYK Zornitza Stark reviewed gene: SYK: Rating: GREEN; Mode of pathogenicity: None; Publications: 33782605; Phenotypes: Immune dysregulation and systemic inflammation; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v3.1018 NCDN Zornitza Stark gene: NCDN was added
gene: NCDN was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: NCDN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NCDN were set to 33711248
Phenotypes for gene: NCDN were set to Intellectual disability; epilepsy
Review for gene: NCDN was set to GREEN
Added comment: Four families reported, all with de novo missense variants except for 1 consanguineous family where 3 affecteds were homozygous and carrier parents unaffected. ID ranged from mild to severe, several had seizures. Green for mono-allelic disease, Red for bi-allelic.
Sources: Literature
Childhood onset dystonia or chorea or related movement disorder v1.90 TSPOAP1 Zornitza Stark gene: TSPOAP1 was added
gene: TSPOAP1 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature
Mode of inheritance for gene: TSPOAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSPOAP1 were set to 33539324
Phenotypes for gene: TSPOAP1 were set to Dystonia, intellectual disability and cerebellar atrophy
Review for gene: TSPOAP1 was set to GREEN
Added comment: 7 affecteds from 3 families (1 consanguineous)
2x null, 1x missense

Affecteds with the null variants presented with juvenile-onset progressive generalized dystonia, associated with intellectual disability and cerebellar atrophy while those with the missense p.(Gly1808Ser) presented with isolated adult-onset focal dystonia (mild cognitive impairment noted). Mouse model.
Sources: Literature
Mitochondrial disorders v2.24 NDUFA12 Zornitza Stark reviewed gene: NDUFA12: Rating: GREEN; Mode of pathogenicity: None; Publications: 33715266; Phenotypes: Mitochondrial complex I deficiency, nuclear type 23 MIM#618244; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v3.91 FBN2 Zornitza Stark reviewed gene: FBN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33571691; Phenotypes: Contractural arachnodactyly, congenital MIM#121050; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mitochondrial disorders v2.24 NDUFB7 Zornitza Stark reviewed gene: NDUFB7: Rating: AMBER; Mode of pathogenicity: None; Publications: 33502047, 27626371; Phenotypes: Congenital lactic acidosis, hypertrophic cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1018 CDH11 Zornitza Stark reviewed gene: CDH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 33811546, 27431290, 28988429, 29271567, 33811546; Phenotypes: Elsahy-Waters syndrome, MIM# 211380, Teebi hypertelorism syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v2.87 NMNAT1 Zornitza Stark gene: NMNAT1 was added
gene: NMNAT1 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: NMNAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NMNAT1 were set to 32533184
Phenotypes for gene: NMNAT1 were set to Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual disability, and Leber congenital amaurosis (SHILCA), MIM#619260
Review for gene: NMNAT1 was set to GREEN
gene: NMNAT1 was marked as current diagnostic
Added comment: The association with LCA is well established.

New report of a syndromic LCA disorder and note also unusual variant type. Three families, but two are distantly related (shared haplotype). The affected children in those two families were homozygous for 7.4-kb duplication involving the last 2 exons of the NMNAT1 gene, spanning the beginning of intron 3 to the middle of the 3-prime UTR (chr1:10,036,359-10,043,727, GRCh37). The third affected individual was compound het for the duplication and a splicing variant.
Sources: Literature
Primary lymphoedema v2.8 RORC Zornitza Stark gene: RORC was added
gene: RORC was added to Primary lymphoedema. Sources: Literature
Mode of inheritance for gene: RORC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RORC were set to 32960152
Phenotypes for gene: RORC were set to Lymphoedema
Review for gene: RORC was set to AMBER
Added comment: Two individuals reported with LoF variants as part of a large cohort. Note gene is depleted for LoF in gnomad, and bi-allelic variants have been associated with immunodeficiency. Moderate/limited evidence for gene-disease association.
Sources: Literature
Primary lymphoedema v2.8 ARAP3 Zornitza Stark gene: ARAP3 was added
gene: ARAP3 was added to Primary lymphoedema. Sources: Literature
Mode of inheritance for gene: ARAP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARAP3 were set to 32908855
Phenotypes for gene: ARAP3 were set to Lymphoedema
Review for gene: ARAP3 was set to AMBER
Added comment: Three unrelated families reported with rare missense variants in this gene as part of a lymphoedema cohort. However, incomplete information regarding segregation and no supporting functional data.
Sources: Literature
Cardiomyopathies - including childhood onset v1.30 MCM10 Zornitza Stark gene: MCM10 was added
gene: MCM10 was added to Cardiomyopathies - including childhood onset. Sources: Literature
Mode of inheritance for gene: MCM10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM10 were set to 33712616
Phenotypes for gene: MCM10 were set to Restrictive cardiomyopathy
Review for gene: MCM10 was set to RED
Added comment: PMID 33712616: three affected sibs with restrictive cardiomyopathy and hypoplasia of the spleen and thymus. Functional data suggested that MCM10 deficiency causes chronic replication stress that reduces cell viability due to increased genomic instability and telomere erosion.
Sources: Literature
Malformations of cortical development v2.44 ATP1A3 Zornitza Stark gene: ATP1A3 was added
gene: ATP1A3 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: ATP1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP1A3 were set to 33762331
Phenotypes for gene: ATP1A3 were set to Polymicrogyria; epilepsy; developmental delay
Review for gene: ATP1A3 was set to GREEN
gene: ATP1A3 was marked as current diagnostic
Added comment: Eight individuals with de novo variants reported and a phenotype distinct from those previously reported in association with this gene.
Sources: Literature
Primary ovarian insufficiency v1.22 HSF2BP Zornitza Stark gene: HSF2BP was added
gene: HSF2BP was added to Primary ovarian insufficiency. Sources: Literature
Mode of inheritance for gene: HSF2BP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSF2BP were set to 32845237
Phenotypes for gene: HSF2BP were set to Premature ovarian failure, OMIM#619245
Review for gene: HSF2BP was set to RED
Added comment: Single family reported where homozygous missense variant segregated with POF in three sisters.
Sources: Literature
Malformations of cortical development v2.44 SLC35A2 Zornitza Stark changed review comment from: >20 individuals reported. However note variants were identified on deep sequencing of affected tissue, and are somatic.
Sources: Literature; to: >20 individuals reported. However note variants were identified on deep sequencing of affected tissue, and are somatic. Rated as Amber as uncertain whether panel only caters to germline sequencing.
Sources: Literature
Malformations of cortical development v2.44 SLC35A2 Zornitza Stark gene: SLC35A2 was added
gene: SLC35A2 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: SLC35A2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SLC35A2 were set to 33407896
Phenotypes for gene: SLC35A2 were set to Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE)
Review for gene: SLC35A2 was set to AMBER
Added comment: >20 individuals reported. However note variants were identified on deep sequencing of affected tissue, and are somatic.
Sources: Literature
Primary immunodeficiency v2.413 IL37 Zornitza Stark gene: IL37 was added
gene: IL37 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: IL37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL37 were set to 33674380
Phenotypes for gene: IL37 were set to Infantile inflammatory bowel disease
Review for gene: IL37 was set to RED
Added comment: Single family reported with homozygous truncating variant this gene and infantile-onset of IBD, some functional data.
Sources: Literature
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.114 ABCC9 Ivone Leong Phenotypes for gene: ABCC9 were changed from Hypertrichotic osteochondrodysplasia, MIM# 239850; Cantu syndrome to Hypertrichotic osteochondrodysplasia, OMIM:239850; Cantu syndrome
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.113 ASXL2 Ivone Leong Publications for gene: ASXL2 were set to 27693232
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.112 PDGFRB Ivone Leong Classified gene: PDGFRB as Green List (high evidence)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.112 PDGFRB Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene has been given a Green rating.
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.112 PDGFRB Ivone Leong Gene: pdgfrb has been classified as Green List (High Evidence).
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.111 PDGFRB Ivone Leong Phenotypes for gene: PDGFRB were changed from Kosaki overgrowth syndrome, MIM# 616592 to Kosaki overgrowth syndrome, OMIM:616592
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.110 PIK3CA Ivone Leong Classified gene: PIK3CA as Green List (high evidence)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.110 PIK3CA Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green based on expert reviews. This gene is associated with a relevant phenotype in OMIM and Gen2Phenotype.
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.110 PIK3CA Ivone Leong Gene: pik3ca has been classified as Green List (High Evidence).
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.109 PIK3CA Ivone Leong Phenotypes for gene: PIK3CA were changed from Human overgrowth syndrome type; Overgrowth with Intellectual disability to Human overgrowth syndrome type; Overgrowth with Intellectual disability; CLOVES: CONGENITAL LIPOMATOUS OVERGROWTH, VASCULAR MALFORMATIONS, AND EPIDERMAL NEVI
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.108 PIK3CA Ivone Leong Mode of inheritance for gene: PIK3CA was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.107 RNF125 Ivone Leong Classified gene: RNF125 as Green List (high evidence)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.107 RNF125 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene has been given a Green rating.
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.107 RNF125 Ivone Leong Gene: rnf125 has been classified as Green List (High Evidence).
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.106 RNF125 Ivone Leong Phenotypes for gene: RNF125 were changed from Tenorio syndrome, MIM# 616260 to Tenorio syndrome, OMIM:616260
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.105 SETD2 Ivone Leong Classified gene: SETD2 as Green List (high evidence)
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.105 SETD2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene has been given a Green rating.
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.105 SETD2 Ivone Leong Gene: setd2 has been classified as Green List (High Evidence).
Beckwith-Wiedemann syndrome (BWS) and other congenital overgrowth disorders v1.104 SETD2 Ivone Leong Phenotypes for gene: SETD2 were changed from Luscan-Lumish syndrome, 616831 to Luscan-Lumish syndrome, OMIM:616831
Glaucoma (developmental) v1.34 FOXD3 Ivone Leong Classified gene: FOXD3 as Amber List (moderate evidence)
Glaucoma (developmental) v1.34 FOXD3 Ivone Leong Added comment: Comment on list classification: Demoted from Green to Amber. Based on the expert reviews, this gene has been demoted from Green to Amber until new evidence is available.
Glaucoma (developmental) v1.34 FOXD3 Ivone Leong Gene: foxd3 has been classified as Amber List (Moderate Evidence).
Structural eye disease v1.65 LMX1B Ivone Leong Classified gene: LMX1B as Amber List (moderate evidence)
Structural eye disease v1.65 LMX1B Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber. This gene is Green on Glaucoma (developmental) (Version 1.33).

"Glaucoma is a key feature of this condition. Sources: Expert list
Zornitza Stark (Australian Genomics), 2 Aug 2020"

This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Structural eye disease v1.65 LMX1B Ivone Leong Gene: lmx1b has been classified as Amber List (Moderate Evidence).
Structural eye disease v1.64 LMX1B Ivone Leong Phenotypes for gene: LMX1B were changed from Nail-patella syndrome, 161200 to Nail-patella syndrome, OMIM:161200
Structural eye disease v1.63 LMX1B Ivone Leong Tag Q2_21_rating tag was added to gene: LMX1B.
Glaucoma (developmental) v1.33 LMX1B Ivone Leong Classified gene: LMX1B as Green List (high evidence)
Glaucoma (developmental) v1.33 LMX1B Ivone Leong Added comment: Comment on list classification: Promoted from Red to Green. This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene has been given a Green rating.
Glaucoma (developmental) v1.33 LMX1B Ivone Leong Gene: lmx1b has been classified as Green List (High Evidence).
Glaucoma (developmental) v1.32 LMX1B Ivone Leong Phenotypes for gene: LMX1B were changed from Nail-patella syndrome, MIM# 161200 to Nail-patella syndrome, OMIM:161200
Glaucoma (developmental) v1.31 PAX6 Ivone Leong Classified gene: PAX6 as Green List (high evidence)
Glaucoma (developmental) v1.31 PAX6 Ivone Leong Added comment: Comment on list classification: Promoted from Red to Green. There is enough evidence to support a gene-disease association. This gene has been given a Green rating.
Glaucoma (developmental) v1.31 PAX6 Ivone Leong Gene: pax6 has been classified as Green List (High Evidence).
Glaucoma (developmental) v1.30 SH3PXD2B Ivone Leong Classified gene: SH3PXD2B as Green List (high evidence)
Glaucoma (developmental) v1.30 SH3PXD2B Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is also Green on Structural eye disease (Version 1.63). Macrocornea could present with or without glaucoma. There is enough evidence to support a gene-disease association. This gene has been given a Green rating.
Glaucoma (developmental) v1.30 SH3PXD2B Ivone Leong Gene: sh3pxd2b has been classified as Green List (High Evidence).
Glaucoma (developmental) v1.29 SH3PXD2B Ivone Leong Publications for gene: SH3PXD2B were set to
Glaucoma (developmental) v1.28 SH3PXD2B Ivone Leong Phenotypes for gene: SH3PXD2B were changed from Frank-ter Haar syndrome, MIM# 249420 to Frank-ter Haar syndrome, OMIM:249420
Structural eye disease v1.63 CREBBP Ivone Leong Classified gene: CREBBP as Amber List (moderate evidence)
Structural eye disease v1.63 CREBBP Ivone Leong Gene: crebbp has been classified as Amber List (Moderate Evidence).
Structural eye disease v1.62 CREBBP Ivone Leong gene: CREBBP was added
gene: CREBBP was added to Structural eye disease. Sources: Literature
Q2_21_rating tags were added to gene: CREBBP.
Mode of inheritance for gene: CREBBP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CREBBP were set to 25599811
Phenotypes for gene: CREBBP were set to Rubinstein-Taybi syndrome 1, OMIM:180849
Review for gene: CREBBP was set to GREEN
Added comment: This gene is Green on Glaucoma (developmental) (Version 1.27).

"Glaucoma is a feature of this syndrome. Sources: Expert list
Zornitza Stark (Australian Genomics), 2 Aug 2020"

This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be given a Green rating at the next review.
Sources: Literature
Glaucoma (developmental) v1.27 CREBBP Ivone Leong Classified gene: CREBBP as Green List (high evidence)
Glaucoma (developmental) v1.27 CREBBP Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene has been given a Green rating.
Glaucoma (developmental) v1.27 CREBBP Ivone Leong Gene: crebbp has been classified as Green List (High Evidence).
Glaucoma (developmental) v1.26 CREBBP Ivone Leong Publications for gene: CREBBP were set to
Glaucoma (developmental) v1.25 CREBBP Ivone Leong Phenotypes for gene: CREBBP were changed from Rubinstein Taybi syndrome to Rubinstein-Taybi syndrome 1, OMIM:180849
Structural eye disease v1.61 TEK Ivone Leong Classified gene: TEK as Amber List (moderate evidence)
Structural eye disease v1.61 TEK Ivone Leong Gene: tek has been classified as Amber List (Moderate Evidence).
Structural eye disease v1.60 TEK Ivone Leong gene: TEK was added
gene: TEK was added to Structural eye disease. Sources: Literature
Q2_21_rating tags were added to gene: TEK.
Mode of inheritance for gene: TEK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TEK were set to 27270174
Phenotypes for gene: TEK were set to Glaucoma 3, primary congenital, E, OMIM:617272
Review for gene: TEK was set to GREEN
Added comment: This gene is also Green on the Glaucoma (developmental) (Version 1.24).

"Ten families and a supportive mouse model. Sources: Expert list
Zornitza Stark (Australian Genomics), 2 Aug 2020"

This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene has been given a Green rating.
Sources: Literature
Structural eye disease v1.59 IFIH1 Ivone Leong Classified gene: IFIH1 as Amber List (moderate evidence)
Structural eye disease v1.59 IFIH1 Ivone Leong Gene: ifih1 has been classified as Amber List (Moderate Evidence).
Glaucoma (developmental) v1.24 TEK Ivone Leong Classified gene: TEK as Green List (high evidence)
Glaucoma (developmental) v1.24 TEK Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene has been given a Green rating.
Glaucoma (developmental) v1.24 TEK Ivone Leong Gene: tek has been classified as Green List (High Evidence).
Glaucoma (developmental) v1.23 TEK Ivone Leong Phenotypes for gene: TEK were changed from Glaucoma 3, primary congenital, E, MIM# 617272 to Glaucoma 3, primary congenital, E, OMIM:617272
Structural eye disease v1.58 IFIH1 Ivone Leong gene: IFIH1 was added
gene: IFIH1 was added to Structural eye disease. Sources: Literature
Q2_21_rating tags were added to gene: IFIH1.
Mode of inheritance for gene: IFIH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IFIH1 were set to 29703882; 31898846
Phenotypes for gene: IFIH1 were set to Singleton-Merten syndrome 1, OMIM:182250
Review for gene: IFIH1 was set to GREEN
Added comment: This gene is also Green on the Glaucoma (developmental) (Version 1.22) panel.

"Glaucoma is a feature of this condition. Sources: Expert list
Zornitza Stark (Australian Genomics), 2 Aug 2020"

PMID: 29703882. "4-year-old boy with a diagnosis of AGS, global developmental delay, glucose-6-phosphate dehydrogenase (G6PD) deficiency, patent ductus arteriosus (PDA), congenital glaucoma, and aniridia. Family history was positive for glaucoma, with consanguineously married parents. According to the genetics report, both parents were carriers of congenital glaucoma genes." PMID: 31898846. Glaucoma found as part of the phenotype.

This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support gene-disease association. This gene should be given a Green rating at the next review.
Sources: Literature
Glaucoma (developmental) v1.22 IFIH1 Ivone Leong Classified gene: IFIH1 as Green List (high evidence)
Glaucoma (developmental) v1.22 IFIH1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is enough evidence to support a gene-disease association. This gene has been given a Green rating.
Glaucoma (developmental) v1.22 IFIH1 Ivone Leong Gene: ifih1 has been classified as Green List (High Evidence).
Glaucoma (developmental) v1.21 IFIH1 Ivone Leong Added comment: Comment on publications: PMID: 29703882. "4-year-old boy with a diagnosis of AGS, global developmental delay, glucose-6-phosphate dehydrogenase (G6PD) deficiency, patent ductus arteriosus (PDA), congenital glaucoma, and aniridia. Family history was positive for glaucoma, with consanguineously married parents. According to the genetics report, both parents were carriers of congenital glaucoma genes."

PMID: 31898846. Glaucoma found as part of the phenotype.
Glaucoma (developmental) v1.21 IFIH1 Ivone Leong Publications for gene: IFIH1 were set to
Glaucoma (developmental) v1.20 IFIH1 Ivone Leong Phenotypes for gene: IFIH1 were changed from Singleton-Merten syndrome 1, MIM# 182250 to Singleton-Merten syndrome 1, OMIM:182250
Structural eye disease v1.57 OCRL Ivone Leong commented on gene: OCRL: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. Glaucoma is present in ~50% of cases, GeneReviews. Therefore this gene should be promoted to Green status at the next review.
Structural eye disease v1.57 OCRL Ivone Leong Tag Q2_21_rating tag was added to gene: OCRL.
Structural eye disease v1.57 OCRL Ivone Leong Phenotypes for gene: OCRL were changed from Lowe syndrome, 309000 to Lowe syndrome, OMIM:309000
Glaucoma (developmental) v1.19 OCRL Ivone Leong Classified gene: OCRL as Green List (high evidence)
Glaucoma (developmental) v1.19 OCRL Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green. This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association, therefore this gene has been promoted to Green.
Glaucoma (developmental) v1.19 OCRL Ivone Leong Gene: ocrl has been classified as Green List (High Evidence).
Glaucoma (developmental) v1.18 OCRL Ivone Leong Phenotypes for gene: OCRL were changed from Lowe syndrome, MIM# 309000 to Lowe syndrome, OMIM:309000
Glaucoma (developmental) v1.17 OCRL Ivone Leong Publications for gene: OCRL were set to
Glaucoma (developmental) v1.16 SBF2 Ivone Leong Classified gene: SBF2 as Green List (high evidence)
Glaucoma (developmental) v1.16 SBF2 Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green. This gene is also Green on the Structural eye disease panel (Version 1.56).
Glaucoma (developmental) v1.16 SBF2 Ivone Leong Gene: sbf2 has been classified as Green List (High Evidence).
Glaucoma (developmental) v1.14 SBF2 Ivone Leong Phenotypes for gene: SBF2 were changed from Charcot-Marie-Tooth disease, type 4B2 604563; CMT with early onset glaucoma to Charcot-Marie-Tooth disease, type 4B2, OMIM:604563; CMT with early onset glaucoma
Glaucoma (developmental) v1.13 SBF2 Ivone Leong Publications for gene: SBF2 were set to
Familial non syndromic congenital heart disease v1.60 ADAMTS19 Ivone Leong Classified gene: ADAMTS19 as Green List (high evidence)
Familial non syndromic congenital heart disease v1.60 ADAMTS19 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene is therefore given a Green rating.
Familial non syndromic congenital heart disease v1.60 ADAMTS19 Ivone Leong Gene: adamts19 has been classified as Green List (High Evidence).
Familial non syndromic congenital heart disease v1.59 ADAMTS19 Ivone Leong Phenotypes for gene: ADAMTS19 were changed from Non-syndromic heart valve disease to Non-syndromic heart valve disease; heart valve disease, MONDO:0002869
Familial non syndromic congenital heart disease v1.58 ADAMTS19 Ivone Leong Publications for gene: ADAMTS19 were set to 31844321
Thoracic aortic aneurysm and dissection v1.7 THSD4 Ivone Leong Classified gene: THSD4 as Amber List (moderate evidence)
Thoracic aortic aneurysm and dissection v1.7 THSD4 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is no phenotypes associated with this gene in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Thoracic aortic aneurysm and dissection v1.7 THSD4 Ivone Leong Gene: thsd4 has been classified as Amber List (Moderate Evidence).
Thoracic aortic aneurysm and dissection v1.6 THSD4 Ivone Leong Tag Q2_21_rating tag was added to gene: THSD4.
Thoracic aortic aneurysm and dissection v1.6 THSD4 Ivone Leong Phenotypes for gene: THSD4 were changed from Thoracic aortic aneurysm and dissection (TAAD) to familial thoracic aortic aneurysm and aortic dissection, MONDO:0019625
Thoracic aortic aneurysm and dissection v1.5 HEY2 Ivone Leong Classified gene: HEY2 as Red List (low evidence)
Thoracic aortic aneurysm and dissection v1.5 HEY2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is not enough evidence to support a gene-disease association. This gene has been given a Red rating.
Thoracic aortic aneurysm and dissection v1.5 HEY2 Ivone Leong Gene: hey2 has been classified as Red List (Low Evidence).
Thoracic aortic aneurysm and dissection v1.4 HEY2 Ivone Leong Phenotypes for gene: HEY2 were changed from congenital heart defects and thoracic aortic aneurysms to congenital heart defects, multiple type, MONDO:0000119; thoracic aortic aneurysm, MONDO:0005396
Pulmonary arterial hypertension v2.13 KDR Ivone Leong edited their review of gene: KDR: Added comment: This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. This gene is also identified as a novel PAH disease gene in PMID:29650961, which was found in 4 cases and 0 in controls. Clingen has curated this gene-disease association and given it a Strong rating. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.; Changed rating: GREEN
Pulmonary arterial hypertension v2.13 KDR Ivone Leong Tag watchlist was removed from gene: KDR.
Tag Q2_21_rating tag was added to gene: KDR.
Pulmonary arterial hypertension v2.13 KDR Ivone Leong Publications for gene: KDR were set to 31980491; 32880713; 33320693
Pulmonary arterial hypertension v2.12 KDR Ivone Leong Phenotypes for gene: KDR were changed from Pulmonary hypertension to Heritable pulmonary arterial hypertension, MONDO:0017148
Pulmonary arterial hypertension v2.11 KDR Ivone Leong Publications for gene: KDR were set to 31980491; 32880713
Pulmonary arterial hypertension v2.10 AQP1 Ivone Leong Tag watchlist tag was added to gene: AQP1.
Pulmonary arterial hypertension v2.10 AQP1 Ivone Leong reviewed gene: AQP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.1018 INPP4A Zornitza Stark reviewed gene: INPP4A: Rating: AMBER; Mode of pathogenicity: None; Publications: 31978615, 31938306, 25338135, 20011524; Phenotypes: Intellectual disability; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathies - including childhood onset v1.30 RHBDF1 Zornitza Stark gene: RHBDF1 was added
gene: RHBDF1 was added to Cardiomyopathies - including childhood onset. Sources: Literature
Mode of inheritance for gene: RHBDF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RHBDF1 were set to 32870709
Phenotypes for gene: RHBDF1 were set to Dilated cardiomyopathy
Review for gene: RHBDF1 was set to AMBER
Added comment: Three families reported with homozygous variants in this gene and onset of DCM in infancy/childhood. Two of the families had the same truncating variant, indicative of founder effect, and one family had a homozygous missense variant.
Sources: Literature
Cardiomyopathies - including childhood onset v1.30 MYLK3 Zornitza Stark gene: MYLK3 was added
gene: MYLK3 was added to Cardiomyopathies - including childhood onset. Sources: Literature
Mode of inheritance for gene: MYLK3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYLK3 were set to 29235529; 31244672; 32213617; 32870709
Phenotypes for gene: MYLK3 were set to Dilated cardiomyopathy
Review for gene: MYLK3 was set to AMBER
Added comment: Two families reported with mono-allelic variants (one extension, one frameshift), and three consanguineous families reported with bi-allelic variants (two hmz frameshift, one hmz missense). Supportive mouse models.
Sources: Literature
Pulmonary arterial hypertension v2.10 AQP1 Ivone Leong Phenotypes for gene: AQP1 were changed from Heritable pulmonary arterial hypertension; HPAH to Heritable pulmonary arterial hypertension, HPAH, MONDO:0017148
Dilated cardiomyopathy - adult and teen v1.19 FLII Ivone Leong Classified gene: FLII as Amber List (moderate evidence)
Dilated cardiomyopathy - adult and teen v1.19 FLII Ivone Leong Gene: flii has been classified as Amber List (Moderate Evidence).
Dilated cardiomyopathy - adult and teen v1.18 FLII Ivone Leong gene: FLII was added
gene: FLII was added to Dilated cardiomyopathy - adult and teen. Sources: Literature
Q2_21_rating tags were added to gene: FLII.
Mode of inheritance for gene: FLII was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLII were set to 32870709
Phenotypes for gene: FLII were set to Dilated cardiomyopathy, MONDO:0005021
Review for gene: FLII was set to GREEN
Added comment: This gene is also on Cardiomyopathies - including childhood onset (Version 1.30).

"Two unrelated families reported with homozygous missense variants in PMID 32870709. Geng (2021): Shown to affect sarcomere size in Drosophila model. FliI knockdown resulted in disorganised myofibrils and increase filamentous actin. Campbell (2002): Hom mice - lethal, het - normal. K/O mouse model of related genes have cytoskeletal actin alterations. No survivors to observed cardiac phenotypes. We are aware of a third family ascertained through our laboratory. Sources: Literature
Zornitza Stark (Australian Genomics), 15 Apr 2021"

This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Sources: Literature
Cardiomyopathies - including childhood onset v1.30 FLII Ivone Leong Classified gene: FLII as Amber List (moderate evidence)
Cardiomyopathies - including childhood onset v1.30 FLII Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Cardiomyopathies - including childhood onset v1.30 FLII Ivone Leong Gene: flii has been classified as Amber List (Moderate Evidence).
Cardiomyopathies - including childhood onset v1.29 FLII Ivone Leong Tag Q2_21_rating tag was added to gene: FLII.
Cardiomyopathies - including childhood onset v1.29 FLII Ivone Leong Phenotypes for gene: FLII were changed from Dilated cardiomyopathy to Dilated cardiomyopathy, MONDO:0005021
Paediatric disorders - additional genes v1.86 PLD1 Ivone Leong commented on gene: PLD1: This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Paediatric disorders - additional genes v1.86 PLD1 Ivone Leong Phenotypes for gene: PLD1 were changed from Cardiac valvular defect, developmental to Cardiac valvular defect, developmental, OMIM:212093
Paediatric disorders - additional genes v1.85 PLD1 Ivone Leong Added comment: Comment on publications: PMID 33645542: 31 individuals from 20 families reported, presenting predominantly with congenital cardiac valve defects and some with neonatal cardiomyopathy. p.I668F is a founder variant among Ashkenazi Jews (allele frequency of ~2%). Sources: Literature
Zornitza Stark (Australian Genomics), 15 Apr 2021
Paediatric disorders - additional genes v1.85 PLD1 Ivone Leong Publications for gene: PLD1 were set to 27799408
Paediatric disorders - additional genes v1.84 PLD1 Ivone Leong Tag Q2_21_rating tag was added to gene: PLD1.
Cardiomyopathies - including childhood onset v1.28 PLD1 Ivone Leong Classified gene: PLD1 as Amber List (moderate evidence)
Cardiomyopathies - including childhood onset v1.28 PLD1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Cardiomyopathies - including childhood onset v1.28 PLD1 Ivone Leong Gene: pld1 has been classified as Amber List (Moderate Evidence).
Cardiomyopathies - including childhood onset v1.27 PLD1 Ivone Leong Tag Q2_21_rating tag was added to gene: PLD1.
Cardiomyopathies - including childhood onset v1.27 PLD1 Ivone Leong Phenotypes for gene: PLD1 were changed from Cardiac valvular defect, developmental, MIM# 212093; neonatal cardiomyopathy to Cardiac valvular defect, developmental, OMIM:212093; neonatal cardiomyopathy
Dilated cardiomyopathy - adult and teen v1.17 RPL3L Ivone Leong Classified gene: RPL3L as Amber List (moderate evidence)
Dilated cardiomyopathy - adult and teen v1.17 RPL3L Ivone Leong Gene: rpl3l has been classified as Amber List (Moderate Evidence).
Dilated cardiomyopathy - adult and teen v1.16 RPL3L Ivone Leong gene: RPL3L was added
gene: RPL3L was added to Dilated cardiomyopathy - adult and teen. Sources: Literature
Q2_21_rating tags were added to gene: RPL3L.
Mode of inheritance for gene: RPL3L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPL3L were set to 32514796; 32870709
Phenotypes for gene: RPL3L were set to Neonatal dilated cardiomyopathy; dilated cardiomyopathy, MONDO:0005021
Review for gene: RPL3L was set to GREEN
Added comment: This gene is also present on the Cardiomyopathies - including childhood onset (Version 1.26) panel.

Review by Zornitza Stark:
"PMID: 32514796 - 5 hom/chet individuals from three independent families who presented with severe neonatal dilated cardiomyopathy. Unaffected sibs were either carriers of a single variant or homozygous wildtype."

This gene is not associated with any phenotypes in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Sources: Literature
Cardiomyopathies - including childhood onset v1.26 RPL3L Ivone Leong Classified gene: RPL3L as Amber List (moderate evidence)
Cardiomyopathies - including childhood onset v1.26 RPL3L Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with any phenotypes in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Cardiomyopathies - including childhood onset v1.26 RPL3L Ivone Leong Gene: rpl3l has been classified as Amber List (Moderate Evidence).
Cardiomyopathies - including childhood onset v1.25 RPL3L Ivone Leong Tag Q2_21_rating tag was added to gene: RPL3L.
Cardiomyopathies - including childhood onset v1.25 RPL3L Ivone Leong Phenotypes for gene: RPL3L were changed from Neonatal dilated cardiomyopathy to Neonatal dilated cardiomyopathy; dilated cardiomyopathy, MONDO:0005021
Cardiomyopathies - including childhood onset v1.24 MIB1 Ivone Leong commented on gene: MIB1: This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. This gene has been tagged and will be submitted to the GMS specialist group for review.
Cardiomyopathies - including childhood onset v1.24 MIB1 Ivone Leong Phenotypes for gene: MIB1 were changed from Left ventricular noncompaction 7 to Left ventricular noncompaction 7, OMIM:615092
Cardiomyopathies - including childhood onset v1.23 MIB1 Ivone Leong Publications for gene: MIB1 were set to
Cardiomyopathies - including childhood onset v1.22 MIB1 Ivone Leong Tag Q2_21_rating tag was added to gene: MIB1.
Tag Q2_21_NHS_review tag was added to gene: MIB1.
Cardiomyopathies - including childhood onset v1.22 COX6B1 Ivone Leong commented on gene: COX6B1: This gene is associated with a phenotype in OMIM and Gene2Phenotype. Currently, there is not enough evidence to support a gene-disease association. It is recommended that this gene should be demoted to Amber/Red at the next review.
Cardiomyopathies - including childhood onset v1.22 COX6B1 Ivone Leong Tag Q2_21_rating tag was added to gene: COX6B1.
Cardiomyopathies - including childhood onset v1.22 COX14 Ivone Leong Phenotypes for gene: COX14 were changed from ?Mitochondrial complex IV deficiency, 220110 to ?Mitochondrial complex IV deficiency, OMIM:220110
Cardiomyopathies - including childhood onset v1.21 COX14 Ivone Leong Tag Q2_21_rating tag was added to gene: COX14.
Cardiomyopathies - including childhood onset v1.21 COX14 Ivone Leong commented on gene: COX14: This gene is associated with a phenotype in OMIM and Gene2Phenotype. Currently, there is not enough evidence to support a gene-disease association. It is recommended that this gene should be demoted to Amber/Red at the next review.
Cardiomyopathies - including childhood onset v1.21 COX14 Ivone Leong Publications for gene: COX14 were set to
Ataxia and cerebellar anomalies - narrow panel v2.110 MSTO1 Sarah Leigh Tag Q2_21_rating tag was added to gene: MSTO1.
Ataxia and cerebellar anomalies - narrow panel v2.110 MSTO1 Sarah Leigh edited their review of gene: MSTO1: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least eight variants reported in five unrelated cases of recessive Myopathy, mitochondrial, and ataxia and one variant reported in dominant Myopathy, mitochondrial, and ataxia in one family, together with supportive functional studies (PMID 28554942).; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.110 MSTO1 Sarah Leigh Classified gene: MSTO1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.110 MSTO1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.110 MSTO1 Sarah Leigh Gene: msto1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v2.24 MSTO1 Sarah Leigh Phenotypes for gene: MSTO1 were changed from Myopathy, mitochondrial, and ataxia, 617675 to Myopathy, mitochondrial, and ataxia OMIM:617675; mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome MONDO:0044714
Hereditary ataxia - adult onset v2.40 MSTO1 Sarah Leigh Phenotypes for gene: MSTO1 were changed from Mitochondrial myopathy and ataxia, 617675 to Myopathy, mitochondrial, and ataxia OMIM:617675; mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome MONDO:0044714
Inborn errors of metabolism v2.111 MSTO1 Sarah Leigh Phenotypes for gene: MSTO1 were changed from Myopathy, mitochondrial, and ataxia, 617675 to Myopathy, mitochondrial, and ataxia OMIM:617675; mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome MONDO:0044714
Possible mitochondrial disorder - nuclear genes v1.40 MSTO1 Sarah Leigh Phenotypes for gene: MSTO1 were changed from Myopathy, mitochondrial, and ataxia, 617675 to Myopathy, mitochondrial, and ataxia OMIM:617675; mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome MONDO:0044714
Congenital muscular dystrophy v2.7 MSTO1 Sarah Leigh changed review comment from: Comment on phenotypes: Myopathy, mitochondrial, and ataxia OMIM:617675; mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome MONDO:0044714
Congenital muscular dystrophy with Brain involvment; to: Comment on phenotypes:
Congenital muscular dystrophy with Brain involvment
Congenital muscular dystrophy v2.7 MSTO1 Sarah Leigh Added comment: Comment on phenotypes: Myopathy, mitochondrial, and ataxia OMIM:617675; mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome MONDO:0044714
Congenital muscular dystrophy with Brain involvment
Congenital muscular dystrophy v2.7 MSTO1 Sarah Leigh Phenotypes for gene: MSTO1 were changed from Congenital muscular dystrophy with Brain involvment; Myopathy, mitochondrial, and ataxia, 617675 to Myopathy, mitochondrial, and ataxia OMIM:617675; mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome MONDO:0044714
Ataxia and cerebellar anomalies - narrow panel v2.109 MSTO1 Sarah Leigh Phenotypes for gene: MSTO1 were changed from Myopathy, mitochondrial, and ataxia, MIM# 617675 to Myopathy, mitochondrial, and ataxia OMIM:617675; mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome MONDO:0044714
Hearing loss v2.160 LOXHD1 Arina Puzriakova Publications for gene: LOXHD1 were set to PMID:16936105; 19732867; 21465660; 22341973
Hearing loss v2.159 LOXHD1 Arina Puzriakova Phenotypes for gene: LOXHD1 were changed from Nonsyndromic Hearing Loss, Recessive; Deafness, autosomal recessive 77, 613079; hearing loss to Deafness, autosomal recessive 77, OMIM:613079
Intellectual disability v3.1018 LOXHD1 Arina Puzriakova Mode of inheritance for gene: LOXHD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Genetic epilepsy syndromes v2.323 KCNH1 Arina Puzriakova Classified gene: KCNH1 as Amber List (moderate evidence)
Genetic epilepsy syndromes v2.323 KCNH1 Arina Puzriakova Added comment: Comment on list classification: Sufficient number of unrelated cases (>3) of epilepsy in patients with variants in the KCNH1 gene. Inclusion on this panel would be of particular benefit to individuals without typical gingival and/or nail anomalies and only mild developmental delays - who may not be tested under other panels (e.g. Limb disorders, ID) and thus may otherwise be missed in analysis.
Genetic epilepsy syndromes v2.323 KCNH1 Arina Puzriakova Gene: kcnh1 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v2.322 KCNH1 Arina Puzriakova gene: KCNH1 was added
gene: KCNH1 was added to Genetic epilepsy syndromes. Sources: Literature
Q2_21_rating tags were added to gene: KCNH1.
Mode of inheritance for gene: KCNH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNH1 were set to 18203178; 20009591; 20683999; 21626675; 23994350; 25420144; 33811134
Phenotypes for gene: KCNH1 were set to Temple-Baraitser syndrome, OMIM:611816; Zimmermann-Laband syndrome 1, OMIM:135500; Intellectual disability; Encephalopathy without features of TBS/ZLS
Review for gene: KCNH1 was set to GREEN
Added comment: Well-established cause of Temple-Baraitser syndrome (MIM #611816) and Zimmermann-Laband syndrome (MIM #135500) characterised by ID with or without epilepsy, hypertrichosis and distinctive features such as gingival hyperplasia and nail hypoplasia/aplasia. Overall, sufficient number of cases with epilepsy to rate Green on this panel (PMIDs: 18203178; 20009591; 20683999; 21626675; 23994350; 25420144)

- PMID: 33811134 (2021) - 7 patients with de novo KCNH1 variants presenting mild/moderate to severe DD/ID, but without any distinctive features of TBS/ZLS such as gingival hyperplasia and nail anomalies. Four patients had epilepsy starting in infancy, with generalised tonic–clonic (4/4), myoclonic (2/4), focal motor (2/4) and tonic (1/4) seizures. One patient experienced status epilepticus. Epilepsy was pharmacoresponsive in all individuals. This study provides evidence of KCNH-related encephalopathy even without the presence of other extra-neurological symptoms that are typically associated with pathogenic variants in this gene.
Sources: Literature
Dilated cardiomyopathy - adult and teen v1.15 NRAP Zornitza Stark reviewed gene: NRAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 33534821, 30384889, 28611399, 32870709; Phenotypes: Dilated cardiomyopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency v2.413 MPEG1 Zornitza Stark gene: MPEG1 was added
gene: MPEG1 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: MPEG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MPEG1 were set to 33224153; 33692780; 28422754
Phenotypes for gene: MPEG1 were set to Immunodeficiency 77, MIM# 619223
Review for gene: MPEG1 was set to GREEN
gene: MPEG1 was marked as current diagnostic
Added comment: Immunodeficiency-77 (IMD77) is an immunologic disorder characterized by recurrent and persistent polymicrobial infections with multiple unusual organisms. Skin and pulmonary infections are the most common, consistent with increased susceptibility to epithelial cell infections. The age at onset is highly variable: some patients have recurrent infections from childhood, whereas others present in late adulthood. The limited number of reported patients are all female, suggesting incomplete penetrance or a possible sex-influenced trait. Patient cells, mainly macrophages, show impaired killing of intracellular bacteria and organisms, including nontubercular mycobacteria, although there is also impaired killing of other organisms, such as Pseudomonas, Candida, and Aspergillus.

Four individuals reported, functional data, including animal model.
Sources: Literature
Ichthyosis and erythrokeratoderma v1.60 ALDH1L2 Zornitza Stark gene: ALDH1L2 was added
gene: ALDH1L2 was added to Ichthyosis and erythrokeratoderma. Sources: Literature
Mode of inheritance for gene: ALDH1L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH1L2 were set to 31341639; 33168096
Phenotypes for gene: ALDH1L2 were set to pruritic ichthyosis, severe diffuse hypomyelination seen on MRI, and abnormal lipid peaks
Review for gene: ALDH1L2 was set to RED
Added comment: Individual reported with bialleleic ALDH1L2 variants (non-canonical splice and a frameshift mutation), who also has a de novo hemizygous RPS6KA3 frameshift mutation. Authors state that not all features of the individual could be explained by the RPS6KA3 variant, and that consideration of Coffin-Lowry sysndrome was only made after identification of the RPS6KA3 variant. Therefore individual has there is a blended phenotype of Coffin–Lowry syndrome and Sjögren–Larsson syndrome. From functional studies authors propose that the ALDH1L2 loss induces mitochondrial dysfunction due to reduced NADPH and increased oxidative stress (PMID: 31341639). Knockout mouse model was viable and did not show an apparent phenotype, however metabolomic analysis showed vastly changed metabotypes in the liver and plasma in these mice suggesting channeling of fatty acids away from β-oxidation. Authors therefore postulate that the role of ALDH1L2 in the lipid metabolism explains why the loss of this enzyme is associated with neuro-cutaneous disease.
Sources: Literature
Intellectual disability v3.1017 KCNH1 Arina Puzriakova Phenotypes for gene: KCNH1 were changed from Temple-Baraitser syndrome, OMIM:611816; Temple-Baraitser syndrome, MONDO:0012735; Zimmermann-Laband syndrome 1, OMIM:135500; Zimmermann-Laband syndrome 1, MONDO:0024526 to Temple-Baraitser syndrome, OMIM:611816; Zimmermann-Laband syndrome 1, OMIM:135500; Intellectual disability; Encephalopathy without features of TBS/ZLS
Intellectual disability v3.1016 KCNH1 Arina Puzriakova Publications for gene: KCNH1 were set to 25420144; 33594261
Clefting v2.24 ESCO2 Zornitza Stark reviewed gene: ESCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32977150; Phenotypes: Juberg-Hayward syndrome, MIM# 216100, Roberts-SC phocomelia syndrome, MIM#268300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1015 KCNH1 Arina Puzriakova edited their review of gene: KCNH1: Changed phenotypes: Intellectual disability, Encephalopathy without features of TBS/ZLS
Intellectual disability v3.1015 KCNH1 Arina Puzriakova reviewed gene: KCNH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33811134; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v2.177 FAM57B Zornitza Stark reviewed gene: FAM57B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33077892; Phenotypes: Cone–rod dystrophy, Maculopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Cardiomyopathies - including childhood onset v1.20 PDLIM3 Ivone Leong Publications for gene: PDLIM3 were set to 25163546
Cardiomyopathies - including childhood onset v1.19 PDLIM3 Ivone Leong Tag Q2_21_rating tag was added to gene: PDLIM3.
Cardiomyopathies - including childhood onset v1.19 PDLIM3 Ivone Leong edited their review of gene: PDLIM3: Added comment: This gene is not associated with a phenotype in OMIM or Gene2Phenotype. Variants in this gene seem to confer susceptibility to DCM but may not directly cause it (PMID: 17254821; 31424159). Therefore, this gene should be downgraded from Green to Amber/Red.; Changed publications: 17254821, 31424159
Cardiomyopathies - including childhood onset v1.19 FLII Zornitza Stark gene: FLII was added
gene: FLII was added to Cardiomyopathies - including childhood onset. Sources: Literature
Mode of inheritance for gene: FLII was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLII were set to 32870709
Phenotypes for gene: FLII were set to Dilated cardiomyopathy
Review for gene: FLII was set to GREEN
Added comment: Two unrelated families reported with homozygous missense variants in PMID 32870709.

Geng (2021): Shown to affect sarcomere size in Drosophila model. FliI knockdown resulted in disorganised myofibrils and increase filamentous actin.
Campbell (2002): Hom mice - lethal, het - normal. K/O mouse model of related genes have cytoskeletal actin alterations. No survivors to observed cardiac phenotypes.

We are aware of a third family ascertained through our laboratory.
Sources: Literature
Familial pulmonary fibrosis v1.13 ZCCHC8 Zornitza Stark gene: ZCCHC8 was added
gene: ZCCHC8 was added to Familial pulmonary fibrosis. Sources: Literature
Mode of inheritance for gene: ZCCHC8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZCCHC8 were set to 31488579
Phenotypes for gene: ZCCHC8 were set to Pulmonary fibrosis
Review for gene: ZCCHC8 was set to AMBER
Added comment: A missense variant (P186L) segregates over 3 generations in a single family, and supporting in vitro assays and mouse model.
Sources: Literature
Intellectual disability v3.1015 COPB1 Zornitza Stark gene: COPB1 was added
gene: COPB1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: COPB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COPB1 were set to 33632302
Phenotypes for gene: COPB1 were set to Baralle-Macken syndrome, MIM# 619255; Severe intellectual disability; variable microcephaly; cataracts
Review for gene: COPB1 was set to AMBER
Added comment: Two unrelated families, some supportive functional data.
Sources: Literature
Cardiomyopathies - including childhood onset v1.19 PLD1 Zornitza Stark gene: PLD1 was added
gene: PLD1 was added to Cardiomyopathies - including childhood onset. Sources: Literature
Mode of inheritance for gene: PLD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLD1 were set to 27799408; 33645542
Phenotypes for gene: PLD1 were set to Cardiac valvular defect, developmental, MIM# 212093; neonatal cardiomyopathy
Review for gene: PLD1 was set to GREEN
gene: PLD1 was marked as current diagnostic
Added comment: PMID 33645542: 31 individuals from 20 families reported, presenting predominantly with congenital cardiac valve defects and some with neonatal cardiomyopathy. p.I668F is a founder variant among Ashkenazi Jews (allele frequency of ~2%).
Sources: Literature
Dilated Cardiomyopathy and conduction defects v1.68 RAB3GAP2 Ivone Leong Classified gene: RAB3GAP2 as Red List (low evidence)
Dilated Cardiomyopathy and conduction defects v1.68 RAB3GAP2 Ivone Leong Added comment: Comment on list classification: Demoted from Green to Red. There is no evidence to support this gene-disease association.
Dilated Cardiomyopathy and conduction defects v1.68 RAB3GAP2 Ivone Leong Gene: rab3gap2 has been classified as Red List (Low Evidence).
Hypertrophic cardiomyopathy - teen and adult v2.20 JPH2 Ivone Leong commented on gene: JPH2: This gene has been tagged and will be submitted for review by the GMS expert group.
Hypertrophic cardiomyopathy - teen and adult v2.20 JPH2 Ivone Leong Phenotypes for gene: JPH2 were changed from Cardiomyopathy, familial hypertrophic 17 (613873) to Cardiomyopathy, hypertrophic, 17, OMIM:613873
Hypertrophic cardiomyopathy - teen and adult v2.19 JPH2 Ivone Leong Publications for gene: JPH2 were set to 28393127; 17509612; 17476457; 30681346; 23973696; 26869393; 28393127; 30235249
Hypertrophic cardiomyopathy - teen and adult v2.19 JPH2 Ivone Leong Publications for gene: JPH2 were set to 28393127; 17509612; 17476457; 30681346
Hypertrophic cardiomyopathy - teen and adult v2.18 JPH2 Ivone Leong Tag Q2_21_expert_review tag was added to gene: JPH2.
Dilated cardiomyopathy - adult and teen v1.15 TBX5 Ivone Leong Classified gene: TBX5 as Amber List (moderate evidence)
Dilated cardiomyopathy - adult and teen v1.15 TBX5 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support gene-disease association. This gene should be rated Green at the next review.
Dilated cardiomyopathy - adult and teen v1.15 TBX5 Ivone Leong Gene: tbx5 has been classified as Amber List (Moderate Evidence).
Dilated cardiomyopathy - adult and teen v1.14 TBX5 Ivone Leong Tag Q2_21_rating tag was added to gene: TBX5.
Dilated cardiomyopathy - adult and teen v1.14 TBX5 Ivone Leong Phenotypes for gene: TBX5 were changed from Holt-Oram syndrome, 142900; Dilated cardiomyopathy to Holt-Oram syndrome, OMIM:142900; Dilated cardiomyopathy
Ataxia and cerebellar anomalies - narrow panel v2.108 IRF2BPL Sarah Leigh Classified gene: IRF2BPL as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.108 IRF2BPL Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.108 IRF2BPL Sarah Leigh Gene: irf2bpl has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia or chorea or related movement disorder v1.90 IRF2BPL Sarah Leigh Classified gene: IRF2BPL as Amber List (moderate evidence)
Childhood onset dystonia or chorea or related movement disorder v1.90 IRF2BPL Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia or chorea or related movement disorder v1.90 IRF2BPL Sarah Leigh Gene: irf2bpl has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia or chorea or related movement disorder v1.89 IRF2BPL Sarah Leigh Tag Q2_21_rating tag was added to gene: IRF2BPL.
Childhood onset dystonia or chorea or related movement disorder v1.89 IRF2BPL Sarah Leigh reviewed gene: IRF2BPL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Childhood onset dystonia or chorea or related movement disorder v1.89 IRF2BPL Sarah Leigh Phenotypes for gene: IRF2BPL were changed from Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, MIM# 618088 to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures OMIM:618088; neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures MONDO:0060759
Childhood onset dystonia or chorea or related movement disorder v1.88 IRF2BPL Sarah Leigh Publications for gene: IRF2BPL were set to 30057031; 30166628
Ataxia and cerebellar anomalies - narrow panel v2.107 IRF2BPL Sarah Leigh Publications for gene: IRF2BPL were set to 30057031; 30166628
Genetic epilepsy syndromes v2.321 IRF2BPL Sarah Leigh Publications for gene: IRF2BPL were set to 30057031; 28135719; 25363768
Hereditary ataxia - adult onset v2.39 IRF2BPL Sarah Leigh Publications for gene: IRF2BPL were set to
Intellectual disability v3.1015 IRF2BPL Sarah Leigh Phenotypes for gene: IRF2BPL were changed from Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures; Global developmental delay, Developmental regression, Seizures, Ataxia to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures OMIM:618088; neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures MONDO:0060759
Hereditary ataxia - adult onset v2.38 IRF2BPL Sarah Leigh Phenotypes for gene: IRF2BPL were changed from Neurodevelopmental disorder with regression, abnormal movement, loss of speech and seizures, 618088 to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures OMIM:618088; neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures MONDO:0060759
Genetic epilepsy syndromes v2.320 IRF2BPL Sarah Leigh Phenotypes for gene: IRF2BPL were changed from Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures 618088 to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures OMIM:618088; neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures MONDO:0060759
Arthrogryposis v3.91 STAC3 Arina Puzriakova Publications for gene: STAC3 were set to 23736855
Ataxia and cerebellar anomalies - narrow panel v2.106 IRF2BPL Sarah Leigh Publications for gene: IRF2BPL were set to 30057031
Ataxia and cerebellar anomalies - narrow panel v2.105 IRF2BPL Sarah Leigh reviewed gene: IRF2BPL: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Laterality disorders and isomerism v1.43 NODAL Ivone Leong Publications for gene: NODAL were set to 19064609
Arthrogryposis v3.90 UNC50 Arina Puzriakova Classified gene: UNC50 as Red List (low evidence)
Arthrogryposis v3.90 UNC50 Arina Puzriakova Added comment: Comment on list classification: Rating Red awaiting further evidence. Only a single variant described in 2 individuals (PMIDs: 29016857; 33820833). Additional cases with different variants or strong functional support required to validate pathogenicity.
Arthrogryposis v3.90 UNC50 Arina Puzriakova Gene: unc50 has been classified as Red List (Low Evidence).
Arthrogryposis v3.89 UNC50 Arina Puzriakova Classified gene: UNC50 as Amber List (moderate evidence)
Arthrogryposis v3.89 UNC50 Arina Puzriakova Gene: unc50 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.105 IRF2BPL Sarah Leigh Phenotypes for gene: IRF2BPL were changed from Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, MIM# 618088 to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures OMIM:618088; neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures MONDO:0060759
Arthrogryposis v3.88 UNC50 Arina Puzriakova gene: UNC50 was added
gene: UNC50 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: UNC50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNC50 were set to 29016857; 33820833
Phenotypes for gene: UNC50 were set to Arthrogryposis multiplex congenita
Review for gene: UNC50 was set to AMBER
Added comment: UNC50 is currently not associated with any phenotype in OMIM (last edited on 02/01/2018) or Gene2Phenotype.

- PMID: 29016857 (2017) - Homozygosity mapping of disease loci combined with WES in a single male from a consanguineous family presenting with lethal AMC revealed a homozygous frameshift deletion in UNC50 gene (c.750_751del:p.Cys251Phefs*4). Functional studies in C. elegans showed the variant caused loss of acetylcholine receptor expression in the muscle.

- PMID: 33820833 (2021) - Single individual reported with the same homozygous c.750_751del:p.Cys251Phefs*4 variant in UNC50 as previously described. The case was identified from a cohort of 315 genetically undiagnosed and unrelated AMC families. Arthrogryposis and tetra ventricular dilation were detected prenatally.

-- Note: it isn't definitively clear whether these are different individuals. Both are singleton males born to consanguineous parents, with the same variant and similar phenotype. Also both infants died at 28 w.g. However, the 2021 paper (PMID:33820833) states their patient was selected from a cohort of cases without a molecular diagnosis and indicate the UNC50 gene had already previously been identified in relation to this phenotype, highlighting the earlier paper (PMID:29016857). There is also no mention of tetra ventricular dilation in the first case, so it is likely that these do represent distinct individuals. Additional cases needed to provide clarity.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.104 IRF2BPL Sarah Leigh Tag Q2_21_rating tag was added to gene: IRF2BPL.
Ataxia and cerebellar anomalies - narrow panel v2.104 FBXL4 Sarah Leigh edited their review of gene: FBXL4: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least five variants reported in five unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.104 FBXL4 Sarah Leigh Tag Q2_21_rating tag was added to gene: FBXL4.
Inborn errors of metabolism v2.110 FBXL4 Sarah Leigh Added comment: Comment on phenotypes: fatal encephalopathy, lactic acidosis, and severe MTDNA depletion in muscle.;Disorders of mitochondrial DNA maintenance and integrity
Inborn errors of metabolism v2.110 FBXL4 Sarah Leigh Phenotypes for gene: FBXL4 were changed from fatal encephalopathy, lactic acidosis, and severe MTDNA depletion in muscle.; Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471 to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) OMIM:615471; mitochondrial DNA depletion syndrome 13 MONDO:0014198
Ataxia and cerebellar anomalies - narrow panel v2.104 FBXL4 Sarah Leigh Classified gene: FBXL4 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.104 FBXL4 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.104 FBXL4 Sarah Leigh Gene: fbxl4 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v2.319 FBXL4 Sarah Leigh Added comment: Comment on phenotypes: Seizures
Genetic epilepsy syndromes v2.319 FBXL4 Sarah Leigh Phenotypes for gene: FBXL4 were changed from Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471; Seizures to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) OMIM:615471; mitochondrial DNA depletion syndrome 13 MONDO:0014198
Intellectual disability v3.1014 FBXL4 Sarah Leigh Added comment: Comment on phenotypes: FATAL ENCEPHALOPATHY, LACTIC ACIDOSIS, AND SEVERE MTDNA DEPLETION IN MUSCLE
Intellectual disability v3.1014 FBXL4 Sarah Leigh Phenotypes for gene: FBXL4 were changed from Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471; FATAL ENCEPHALOPATHY, LACTIC ACIDOSIS, AND SEVERE MTDNA DEPLETION IN MUSCLE to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) OMIM:615471; mitochondrial DNA depletion syndrome 13 MONDO:0014198
Mitochondrial disorders v2.23 FBXL4 Sarah Leigh Added comment: Comment on phenotypes: Disorders of mitochondrial DNA maintenance and integrity;Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471;fatal encephalopathy, lactic acidosis, and severe MTDNA depletion in muscle.
Mitochondrial disorders v2.23 FBXL4 Sarah Leigh Phenotypes for gene: FBXL4 were changed from Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471; fatal encephalopathy, lactic acidosis, and severe MTDNA depletion in muscle. to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) OMIM:615471; mitochondrial DNA depletion syndrome 13 MONDO:0014198
Laterality disorders and isomerism v1.42 DNAAF2 Ivone Leong commented on gene: DNAAF2: This gene is associated with a relevant disease in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. Therefore this gene should be rated Green at the next review.
Laterality disorders and isomerism v1.42 DNAAF2 Ivone Leong Tag Q2_21_rating tag was added to gene: DNAAF2.
Laterality disorders and isomerism v1.42 DNAAF2 Ivone Leong Added comment: Comment on publications: PMID: 32638265 is an additional case in a non-consanguineous Han Chinese family. Proband has compound heterozygous variants in this gene and exhibited typical PCD-related clinical symptoms, including chronic otitis media, and recurrent pneumonia since birth. The proband also had chronic ethmoid and maxillary sinusitis, ring-shaped or ductal opacities throughout both lungs, bilateral lung bronchiectasis, and situs inversus totalis in the heart, liver, and colon.
Laterality disorders and isomerism v1.42 DNAAF2 Ivone Leong Publications for gene: DNAAF2 were set to 19052621; 31107948
Ataxia and cerebellar anomalies - narrow panel v2.103 FBXL4 Sarah Leigh Phenotypes for gene: FBXL4 were changed from Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), MIM# 615471 to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) OMIM:615471; mitochondrial DNA depletion syndrome 13 MONDO:0014198
White matter disorders and cerebral calcification - narrow panel v1.38 FA2H Sarah Leigh edited their review of gene: FA2H: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least eight variants reported in seven unrelated cases.; Changed rating: GREEN
White matter disorders and cerebral calcification - narrow panel v1.38 FA2H Sarah Leigh Tag Q2_21_rating tag was added to gene: FA2H.
White matter disorders and cerebral calcification - narrow panel v1.38 FA2H Sarah Leigh Phenotypes for gene: FA2H were changed from to Spastic paraplegia 35, autosomal recessive OMIM:612319; hereditary spastic paraplegia 35 MONDO:0012866
Ataxia and cerebellar anomalies - narrow panel v2.102 FA2H Sarah Leigh Publications for gene: FA2H were set to 31135052
White matter disorders and cerebral calcification - narrow panel v1.37 FA2H Sarah Leigh Publications for gene: FA2H were set to MIM#612319
White matter disorders and cerebral calcification - narrow panel v1.36 FA2H Sarah Leigh Classified gene: FA2H as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.36 FA2H Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
White matter disorders and cerebral calcification - narrow panel v1.36 FA2H Sarah Leigh Gene: fa2h has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.101 FA2H Sarah Leigh Tag Q2_21_rating tag was added to gene: FA2H.
Ataxia and cerebellar anomalies - narrow panel v2.101 FA2H Sarah Leigh edited their review of gene: FA2H: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least eight variants reported in seven unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.101 FA2H Sarah Leigh Classified gene: FA2H as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.101 FA2H Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.101 FA2H Sarah Leigh Gene: fa2h has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.100 FA2H Sarah Leigh Phenotypes for gene: FA2H were changed from Spastic paraplegia 35, autosomal recessive MIM#612319 to Spastic paraplegia 35, autosomal recessive OMIM:612319; hereditary spastic paraplegia 35 MONDO:0012866
Ataxia and cerebellar anomalies - narrow panel v2.99 EBF3 Sarah Leigh edited their review of gene: EBF3: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 10 variants reported in at least 11 unrelated cases.; Changed rating: GREEN
Arthrogryposis v3.87 MAGEL2 Arina Puzriakova Publications for gene: MAGEL2 were set to 26365340; 27195816; 31504653; 29359444; 24076603
Arthrogryposis v3.86 MAGEL2 Arina Puzriakova Phenotypes for gene: MAGEL2 were changed from Schaaf-Yang syndrome, 615547; ARTHROGRYPOSIS MULTIPLEX CONGENITA; Prader-Willi-Like syndrome to Schaaf-Yang syndrome, OMIM:615547; Prader-Willi-Like syndrome
Severe Paediatric Disorders v1.75 EBF3 Sarah Leigh Phenotypes for gene: EBF3 were changed from Hypotonia, ataxia, and delayed development syndrome, 617330 to Hypotonia, ataxia, and delayed development syndrome OMIM:617330; hypotonia, ataxia, and delayed development syndrome MONDO:0015021
Intellectual disability v3.1013 EBF3 Sarah Leigh Phenotypes for gene: EBF3 were changed from Hypotonia, ataxia, and delayed development syndrome 617330 to Hypotonia, ataxia, and delayed development syndrome OMIM:617330; hypotonia, ataxia, and delayed development syndrome MONDO:0015021
Hereditary ataxia - adult onset v2.37 EBF3 Sarah Leigh Phenotypes for gene: EBF3 were changed from Hypotonia, ataxia and delayed development syndrome, 617330 to Hypotonia, ataxia, and delayed development syndrome OMIM:617330; hypotonia, ataxia, and delayed development syndrome MONDO:0015021
DDG2P v2.25 EBF3 Sarah Leigh Added comment: Comment on phenotypes: Intellectual Disability, Ataxia, and Facial Dysmorphism
DDG2P v2.25 EBF3 Sarah Leigh Phenotypes for gene: EBF3 were changed from Intellectual Disability, Ataxia, and Facial Dysmorphism to Hypotonia, ataxia, and delayed development syndrome OMIM:617330; hypotonia, ataxia, and delayed development syndrome MONDO:0015021
Arthrogryposis v3.85 LMOD3 Arina Puzriakova Phenotypes for gene: LMOD3 were changed from Nemaline myopathy 10 616165 to Nemaline myopathy 10, OMIM:616165
Fetal anomalies v1.641 EBF3 Sarah Leigh Added comment: Comment on phenotypes: Intellectual Disability, Ataxia, and Facial Dysmorphism
Fetal anomalies v1.641 EBF3 Sarah Leigh Phenotypes for gene: EBF3 were changed from Intellectual Disability, Ataxia, and Facial Dysmorphism to Hypotonia, ataxia, and delayed development syndrome OMIM:617330; hypotonia, ataxia, and delayed development syndrome MONDO:0015021
Arthrogryposis v3.84 LMOD3 Arina Puzriakova Publications for gene: LMOD3 were set to 25250574
Arthrogryposis v3.83 LGI4 Arina Puzriakova Phenotypes for gene: LGI4 were changed from Arthrogryposis Multiplex Congenita; Arthrogryposis multiplex congenita, neurogenic, with myelin defect, 617468; AMCNMY to Arthrogryposis multiplex congenita 1, neurogenic, with myelin defect, OMIM:617468
Arthrogryposis v3.82 LGI4 Arina Puzriakova Publications for gene: LGI4 were set to 28318499; 15857855; 16341215
Arthrogryposis v3.81 GLDN Arina Puzriakova Phenotypes for gene: GLDN were changed from Lethal congenital contracture syndrome 11 617194 to Lethal congenital contracture syndrome 11, OMIM:617194
Arthrogryposis v3.80 GLDN Arina Puzriakova Publications for gene: GLDN were set to 27616481
Arthrogryposis v3.79 CNTNAP1 Arina Puzriakova Phenotypes for gene: CNTNAP1 were changed from Lethal congenital contracture syndrome 7 616286 to Lethal congenital contracture syndrome 7, OMIM:616286
Arthrogryposis v3.78 CNTNAP1 Arina Puzriakova Publications for gene: CNTNAP1 were set to 24319099
Ataxia and cerebellar anomalies - narrow panel v2.99 EBF3 Sarah Leigh Phenotypes for gene: EBF3 were changed from Hypotonia, ataxia, and delayed development syndrome, MIM# 617330 to Hypotonia, ataxia, and delayed development syndrome OMIM:617330; hypotonia, ataxia, and delayed development syndrome MONDO:0015021
Arthrogryposis v3.77 ADCY6 Arina Puzriakova Publications for gene: ADCY6 were set to 24319099; 26257172; 31846058
Arthrogryposis v3.76 ADCY6 Arina Puzriakova edited their review of gene: ADCY6: Added comment: - PMID: 33820833 (2021) - Further 2 sibs reported with a homozygous c.3346C>T:p.Arg1116Cys variant in the ADCY6 gene. The family was identified from a cohort of 315 genetically undiagnosed and unrelated AMC families. Arthrogryposis and IUGR were detected prenatally.; Changed rating: GREEN; Changed publications: 24319099, 26257172, 31846058, 33820833; Changed phenotypes: Lethal congenital contracture syndrome 8, OMIM:616287; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.98 EBF3 Sarah Leigh Classified gene: EBF3 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.98 EBF3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.98 EBF3 Sarah Leigh Gene: ebf3 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.97 EBF3 Sarah Leigh Tag Q2_21_rating tag was added to gene: EBF3.
Ataxia and cerebellar anomalies - narrow panel v2.97 DOCK3 Sarah Leigh edited their review of gene: DOCK3: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least seven variants reported in at least five unrelated cases.; Changed rating: GREEN
Intellectual disability v3.1012 DOCK3 Sarah Leigh Phenotypes for gene: DOCK3 were changed from Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, 618292 to Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia OMIM:618292; neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia MONDO:0032661
Severe Paediatric Disorders v1.74 DOCK3 Sarah Leigh Phenotypes for gene: DOCK3 were changed from Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, 618292 to Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia OMIM:618292; neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia MONDO:0032661
Ataxia and cerebellar anomalies - narrow panel v2.97 DOCK3 Sarah Leigh Phenotypes for gene: DOCK3 were changed from Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, MIM#618292 to Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia OMIM:618292; neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia MONDO:0032661
Ataxia and cerebellar anomalies - narrow panel v2.96 DOCK3 Sarah Leigh Tag Q2_21_rating tag was added to gene: DOCK3.
Ataxia and cerebellar anomalies - narrow panel v2.96 DOCK3 Sarah Leigh Classified gene: DOCK3 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.96 DOCK3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.96 DOCK3 Sarah Leigh Gene: dock3 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.95 DKC1 Sarah Leigh reviewed gene: DKC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.95 DKC1 Sarah Leigh Publications for gene: DKC1 were set to 9590285; 9886310; 10921354; 33734615; 10583221
Ataxia and cerebellar anomalies - narrow panel v2.94 DKC1 Sarah Leigh Publications for gene: DKC1 were set to 9590285; 9886310; 10921354
Holoprosencephaly v2.16 PLCH1 Arina Puzriakova Classified gene: PLCH1 as Amber List (moderate evidence)
Holoprosencephaly v2.16 PLCH1 Arina Puzriakova Added comment: Comment on list classification: Two unrelated families reported in PMID:33820834 with a holoprosencephaly spectrum phenotype associated with biallelic PLCH1 variants. Rating Amber, awaiting further cases.
Holoprosencephaly v2.16 PLCH1 Arina Puzriakova Gene: plch1 has been classified as Amber List (Moderate Evidence).
Holoprosencephaly v2.15 PLCH1 Arina Puzriakova gene: PLCH1 was added
gene: PLCH1 was added to Holoprosencephaly. Sources: Literature
Mode of inheritance for gene: PLCH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLCH1 were set to 33820834
Phenotypes for gene: PLCH1 were set to Severe developmental delay; Brain malformations; Holoprosencephaly spectrum
Review for gene: PLCH1 was set to AMBER
Added comment: PLCH1 is currently not associated with any phenotype in OMIM (last edited on 16/06/2009) or Gene2Phenotype.

- PMID: 33820834 (2021) - Two sibling pairs from two unrelated families with a holoprosencephaly spectrum phenotype and different homozygous PLCH1 variants (c.2065C>T, p.Arg689* and c.4235delA, p.Cys1079ValfsTer16, respectively). One family presented with congenital hydrocephalus, epilepsy, significant developmental delay and a monoventricle or fused thalami; while sibs from the second family had alobar holoprosencephaly and cyclopia. 3/4 individuals also displayed a cleft palate and congenital heart disease.

Human embryo immunohistochemistry showed PLCH1 to be expressed in the notorcord, developing spinal cord (in a ventral to dorsal gradient), dorsal root ganglia, cerebellum and dermatomyosome.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v2.93 DKC1 Sarah Leigh Phenotypes for gene: DKC1 were changed from X-linked dyskeratosis congenita to Dyskeratosis congenita, X-linked OMIM:305000; dyskeratosis congenita, X-linked MONDO:0010584
Ataxia and cerebellar anomalies - narrow panel v2.92 DKC1 Sarah Leigh Publications for gene: DKC1 were set to 9590285; 9886310
Hereditary spastic paraplegia - adult onset v1.17 CYP2U1 Sarah Leigh Phenotypes for gene: CYP2U1 were changed from Spastic paraplegia 56, autosomal recessive, 615030 to Spastic paraplegia 56, autosomal recessive OMIM:615030; hereditary spastic paraplegia 56 MONDO:0014015
Ataxia and cerebellar anomalies - narrow panel v2.91 CYP2U1 Sarah Leigh Added comment: Comment on phenotypes: Autosomal recessive spastic paraplegia 56 (#615030) complex form of disorder, ataxia not yet identified in affected patients.
Ataxia and cerebellar anomalies - narrow panel v2.91 CYP2U1 Sarah Leigh Phenotypes for gene: CYP2U1 were changed from Autosomal recessive spastic paraplegia 56 (#615030) complex form of disorder, ataxia not yet identified in affected patients. to Spastic paraplegia 56, autosomal recessive OMIM:615030; hereditary spastic paraplegia 56 MONDO:0014015
Ataxia and cerebellar anomalies - narrow panel v2.90 CYP2U1 Sarah Leigh Publications for gene: CYP2U1 were set to
Aniridia v2.14 PAX6 Arina Puzriakova Publications for gene: PAX6 were set to 1302030; 8111379; 7951315; 7666404; 7550230; 19876904; 9931324; 12552561; 11826019; 11553050; 17148041; 17595013; 17406642; 32467297
Adult solid tumours cancer susceptibility v2.9 PALB2 Arina Puzriakova Publications for gene: PALB2 were set to
Genetic epilepsy syndromes v2.318 KCNQ2 Arina Puzriakova Publications for gene: KCNQ2 were set to Dedek et al (2003) Epilepsy Res 54: 21-27
Intellectual disability v3.1011 KCNQ2 Arina Puzriakova Publications for gene: KCNQ2 were set to
Hereditary neuropathy NOT PMP22 copy number v1.25 VWA1 Ian Berry gene: VWA1 was added
gene: VWA1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS
Mode of inheritance for gene: VWA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VWA1 were set to PMID: 33559681
Phenotypes for gene: VWA1 were set to axonal hereditary motor neuropathy; myopathy
Penetrance for gene: VWA1 were set to unknown
Review for gene: VWA1 was set to GREEN
gene: VWA1 was marked as current diagnostic
Added comment: 17 individuals from 15 families, recurrent 10bp repeat allele causative in all patients. Detected in 100K so clearly tractable by WGS.
Sources: NHS GMS
Genetic epilepsy syndromes v2.317 KCNQ2 Arina Puzriakova Phenotypes for gene: KCNQ2 were changed from BENIGN NEONATAL EPILEPSY TYPE 1 (EBN1); EPILEPTIC ENCEPHALOPATHY EARLY INFANTILE TYPE 7 (EIEE7); Epileptic encephalopathy, early infantile, 7; Myokymia; Seizures, benign neonatal, 1 to Developmental and epileptic encephalopathy 7, OMIM:613720; Seizures, benign neonatal, 1, OMIM:121200
Intellectual disability v3.1010 KCNQ2 Arina Puzriakova Phenotypes for gene: KCNQ2 were changed from Seizures, benign neonatal, 1, 121200Myokymia, 121200Epileptic encephalopathy, early infantile, 7, 613720; BENIGN NEONATAL EPILEPSY TYPE 1 (EBN1) to Developmental and epileptic encephalopathy 7, OMIM:613720
Aniridia v2.13 PAX6 Arina Puzriakova Publications for gene: PAX6 were set to 1302030; 8111379; 7951315; 7666404; 7550230; 19876904; 9931324; 12552561; 11826019; 11553050; 17148041; 17595013; 17406642
Inherited pancreatic cancer v1.18 CDKN2A Arina Puzriakova Publications for gene: CDKN2A were set to 30558719
Pigmentary skin disorders v1.10 CDKN2A Arina Puzriakova Phenotypes for gene: CDKN2A were changed from MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2; CMM2; Melanoma susceptibility to {Melanoma, cutaneous malignant, 2}, OMIM:155601; {Melanoma and neural system tumor syndrome}, OMIM:155755; {Melanoma-pancreatic cancer syndrome}, OMIM:606719
Adult solid tumours cancer susceptibility v2.8 CDKN2A Arina Puzriakova Phenotypes for gene: CDKN2A were changed from Familial Malignant Melanoma and Tumors of the Nervous system, Familial Uveal Melanoma to {Melanoma, cutaneous malignant, 2}, OMIM:155601; {Melanoma and neural system tumor syndrome}, OMIM:155755; {Melanoma-pancreatic cancer syndrome}, OMIM:606719
Familial melanoma v1.10 CDKN2A Arina Puzriakova Phenotypes for gene: CDKN2A were changed from to {Melanoma, cutaneous malignant, 2}, OMIM:155601; {Melanoma and neural system tumor syndrome}, OMIM:155755; {Melanoma-pancreatic cancer syndrome}, OMIM:606719
Ataxia and cerebellar anomalies - narrow panel v2.89 CSTB Sarah Leigh Phenotypes for gene: CSTB were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) OMIM:254800; Unverricht-Lundborg syndrome MONDO:0009698
Childhood onset dystonia or chorea or related movement disorder v1.87 CSTB Sarah Leigh Tag Q2_21_phenotype tag was added to gene: CSTB.
Childhood onset dystonia or chorea or related movement disorder v1.87 CSTB Sarah Leigh Phenotypes for gene: CSTB were changed from microcephaly and severe dyskinesia; Epilepsy, progressive myoclonic 1A, 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) OMIM:254800; Unverricht-Lundborg syndrome MONDO:0009698
Ataxia and cerebellar anomalies - narrow panel v2.88 CSTB_CCCCGCCCCGCG Sarah Leigh Phenotypes for STR: CSTB_CCCCGCCCCGCG were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) OMIM:254800; Unverricht-Lundborg syndrome MONDO:0009698
Ataxia and cerebellar anomalies - narrow panel v2.87 CSTB_CCCCGCCCCGCG Sarah Leigh commented on STR: CSTB_CCCCGCCCCGCG
Ataxia and cerebellar anomalies - narrow panel v2.87 CSTB Sarah Leigh edited their review of gene: CSTB: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least five variants reported in at least four unrelated cases. Some cases are compound heterozygous with STR: CSTB_CCCCGCCCCGCG; Changed rating: GREEN
Laterality disorders and isomerism v1.41 NKX2-5 Ivone Leong Added comment: Comment on phenotypes: This gene is also associated with Ventricular septal defect 3, OMIM:614432;Tetralogy of Fallot, OMIM:187500
Laterality disorders and isomerism v1.41 NKX2-5 Ivone Leong Phenotypes for gene: NKX2-5 were changed from Ventricular septal defect 3, OMIM:614432; Tetralogy of Fallot, OMIM:187500 to visceral heterotaxy, MONDO:0018677
Laterality disorders and isomerism v1.40 MYH6 Ivone Leong Added comment: Comment on phenotypes: This gene is also associated with Atrial septal defect 3, OMIM:614089
Laterality disorders and isomerism v1.40 MYH6 Ivone Leong Phenotypes for gene: MYH6 were changed from Atrial septal defect 3, OMIM:614089 to visceral heterotaxy, MONDO:0018677
Laterality disorders and isomerism v1.39 NKX2-5 Ivone Leong Phenotypes for gene: NKX2-5 were changed from to Ventricular septal defect 3, OMIM:614432; Tetralogy of Fallot, OMIM:187500
Laterality disorders and isomerism v1.38 MYH6 Ivone Leong Classified gene: MYH6 as Red List (low evidence)
Laterality disorders and isomerism v1.38 MYH6 Ivone Leong Added comment: Comment on list classification: Downgraded from Amber to Red. There is currently no evidence to support that MYH6 is associated with heterotaxy/laterality defects.
Laterality disorders and isomerism v1.38 MYH6 Ivone Leong Gene: myh6 has been classified as Red List (Low Evidence).
Laterality disorders and isomerism v1.37 MYH6 Ivone Leong Phenotypes for gene: MYH6 were changed from to Atrial septal defect 3, OMIM:614089
Laterality disorders and isomerism v1.36 MYH6 Ivone Leong Publications for gene: MYH6 were set to
Laterality disorders and isomerism v1.35 MYH6 Ivone Leong Mode of inheritance for gene: MYH6 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Laterality disorders and isomerism v1.34 DNAAF2 Ivone Leong Phenotypes for gene: DNAAF2 were changed from Ciliary dyskinesia, primary, 10, 612518 to Ciliary dyskinesia, primary, 10, OMIM:612518
Laterality disorders and isomerism v1.33 DNAAF2 Ivone Leong Publications for gene: DNAAF2 were set to 19052621
Laterality disorders and isomerism v1.32 CFC1 Ivone Leong Tag Q2_21_expert_review tag was added to gene: CFC1.
Laterality disorders and isomerism v1.32 CFC1 Ivone Leong reviewed gene: CFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Laterality disorders and isomerism v1.32 CFC1 Ivone Leong Tag Q2_21_rating tag was added to gene: CFC1.
Laterality disorders and isomerism v1.32 CFC1 Ivone Leong Phenotypes for gene: CFC1 were changed from Heterotaxy, visceral, 2, 605376 to Heterotaxy, visceral, 2, autosomal, OMIM:605376
Laterality disorders and isomerism v1.31 CFC1 Ivone Leong Publications for gene: CFC1 were set to 11062482; 25423076
Laterality disorders and isomerism v1.30 CCDC65 Ivone Leong commented on gene: CCDC65
Ataxia and cerebellar anomalies - narrow panel v2.87 CSTB_CCCCGCCCCGCG Sarah Leigh Publications for STR: CSTB_CCCCGCCCCGCG were set to
Ataxia and cerebellar anomalies - narrow panel v2.86 CSTB Sarah Leigh Publications for gene: CSTB were set to
Ataxia and cerebellar anomalies - narrow panel v2.85 CSTB Sarah Leigh Classified gene: CSTB as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.85 CSTB Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.85 CSTB Sarah Leigh Gene: cstb has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.84 CSTB Sarah Leigh Tag Q2_21_rating tag was added to gene: CSTB.
Laterality disorders and isomerism v1.30 CCDC65 Ivone Leong Phenotypes for gene: CCDC65 were changed from to Ciliary dyskinesia, primary, 27, OMIM:615504
Laterality disorders and isomerism v1.29 CCDC65 Ivone Leong Publications for gene: CCDC65 were set to
Laterality disorders and isomerism v1.28 CCDC65 Ivone Leong Mode of inheritance for gene: CCDC65 was changed from to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.84 COA7 Sarah Leigh edited their review of gene: COA7: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least five variants reported in at least five unrelated cases.; Changed rating: GREEN
White matter disorders and cerebral calcification - narrow panel v1.35 COA7 Sarah Leigh edited their review of gene: COA7: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least five variants reported in at least five unrelated cases.; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.84 COA7 Sarah Leigh Tag Q2_21_rating tag was added to gene: COA7.
White matter disorders and cerebral calcification - narrow panel v1.35 COA7 Sarah Leigh Tag Q2_21_rating tag was added to gene: COA7.
White matter disorders and cerebral calcification - narrow panel v1.35 COA7 Sarah Leigh Classified gene: COA7 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v1.35 COA7 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
White matter disorders and cerebral calcification - narrow panel v1.35 COA7 Sarah Leigh Gene: coa7 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.84 COA7 Sarah Leigh Classified gene: COA7 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.84 COA7 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.84 COA7 Sarah Leigh Gene: coa7 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v1.34 COA7 Sarah Leigh Publications for gene: COA7 were set to 27683825; 29718187
Ataxia and cerebellar anomalies - narrow panel v2.83 COA7 Sarah Leigh Publications for gene: COA7 were set to 29718187; 27683825
Inborn errors of metabolism v2.109 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
Mitochondrial disorder with complex IV deficiency v1.11 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, 618387 to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
White matter disorders and cerebral calcification - narrow panel v1.33 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MIM#618387 to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
Hereditary ataxia - adult onset v2.36 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from Spinocerebellar ataxia with axonal neuropathy to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
Mitochondrial disorders v2.22 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
Hereditary neuropathy v1.384 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, 618387; Cerebellar atrophy, leukoencephalopathy and spinal cord atrophy in some patients. Axonal sensory and motor neuropathy to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
Possible mitochondrial disorder - nuclear genes v1.39 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, 618387 to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
Severe Paediatric Disorders v1.73 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, 618387 to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
Ataxia and cerebellar anomalies - narrow panel v2.82 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, MIM#618387 to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
Intellectual disability v3.1009 FAR1 Arina Puzriakova Publications for gene: FAR1 were set to 0
Genetic epilepsy syndromes v2.316 FAR1 Arina Puzriakova Phenotypes for gene: FAR1 were changed from Peroxisomal fatty acyl-CoA reductase 1 disorder 616154 to Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154
Fetal anomalies v1.640 FAR1 Arina Puzriakova Phenotypes for gene: FAR1 were changed from SEVERE INTELLECTUAL DISABILITY, EPILEPSY, AND CATARACTS to Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154
Inborn errors of metabolism v2.108 FAR1 Arina Puzriakova Phenotypes for gene: FAR1 were changed from Peroxisomal fatty acyl-CoA reductase 1 disorder, 616154 to Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154
Undiagnosed metabolic disorders v1.452 FAR1 Arina Puzriakova Phenotypes for gene: FAR1 were changed from to Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154
Peroxisomal disorders v1.7 FAR1 Arina Puzriakova Phenotypes for gene: FAR1 were changed from Peroxisomal fatty acyl-CoA reductase 1 disorder 616154 to Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154
Intellectual disability v3.1008 FAR1 Arina Puzriakova Phenotypes for gene: FAR1 were changed from SEVERE INTELLECTUAL DISABILITY, EPILEPSY, AND CATARACTS to Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154
Severe Paediatric Disorders v1.72 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from ?Hydrops, lactic acidosis, and sideroblastic anemia, 617021; Perrault syndrome 4, 615300 to Perrault syndrome 4, OMIM:615300; Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021
Mitochondrial disorders v2.21 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Perrault syndrome 4, 615300; Perrault syndrome to Perrault syndrome 4, OMIM:615300; Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only); Multiple respiratory chain complex deficiencies (disorders of protein synthesis
Inborn errors of metabolism v2.107 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from Perrault syndrome; Perrault syndrome 4, 615300; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) to Perrault syndrome 4, OMIM:615300; Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only); Multiple respiratory chain complex deficiencies (disorders of protein synthesis
Possible mitochondrial disorder - nuclear genes v1.38 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from ?Hydrops, lactic acidosis, and sideroblastic anemia, 617021; Perrault syndrome 4, 615300 to Perrault syndrome 4, OMIM:615300; Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only); Multiple respiratory chain complex deficiencies (disorders of protein synthesis
Undiagnosed metabolic disorders v1.451 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Perrault syndrome 4, 615300; Perrault syndrome to Perrault syndrome 4, OMIM:615300; Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only); Multiple respiratory chain complex deficiencies (disorders of protein synthesis
Rare anaemia v1.21 LARS2 Arina Puzriakova Tag Q2_21_rating tag was added to gene: LARS2.
Rare anaemia v1.21 LARS2 Arina Puzriakova reviewed gene: LARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26537577, 32442335; Phenotypes: Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare anaemia v1.21 LARS2 Arina Puzriakova Publications for gene: LARS2 were set to
Rare anaemia v1.20 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from hydrops/sideroblastic anaemia to Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021
Ataxia and cerebellar anomalies - narrow panel v2.81 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from Perrault syndrome 4, MIM# 615300; Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021; Leukodystrophy to Perrault syndrome 4, OMIM:615300
White matter disorders - adult onset v1.8 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from Leukodystrophy to Perrault syndrome 4, OMIM:615300; Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021; Leukodystrophy
Primary ovarian insufficiency v1.22 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from Perrault syndrome 4 615300 to Perrault syndrome 4, OMIM:615300
Fetal hydrops v1.28 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from ?Hydrops, lactic acidosis, and sideroblastic anemia, 617021; HLASA to Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021
Fetal hydrops v1.27 LARS2 Arina Puzriakova Publications for gene: LARS2 were set to 26537577
Fetal hydrops v1.26 LARS2 Arina Puzriakova Classified gene: LARS2 as Green List (high evidence)
Fetal hydrops v1.26 LARS2 Arina Puzriakova Added comment: Comment on list classification: Promoted from Red to Green as there is now a sufficient number of unrelated cases (3) with evidence of fetal hydrops due to biallelic variants in this gene.
Fetal hydrops v1.26 LARS2 Arina Puzriakova Gene: lars2 has been classified as Green List (High Evidence).
Fetal hydrops v1.25 LARS2 Arina Puzriakova reviewed gene: LARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26537577, 32442335; Phenotypes: Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.639 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from PERRAULT SYNDROME to Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021
Fetal anomalies v1.638 LARS2 Arina Puzriakova Publications for gene: LARS2 were set to
Fetal anomalies v1.637 LARS2 Arina Puzriakova Tag Q2_21_rating tag was added to gene: LARS2.
Fetal anomalies v1.637 LARS2 Arina Puzriakova reviewed gene: LARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26537577, 32442335; Phenotypes: Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1007 LARS2 Arina Puzriakova Publications for gene: LARS2 were set to
Intellectual disability v3.1006 LARS2 Arina Puzriakova changed review comment from: Comment on list classification: While are a few cases with neurological symptoms including developmental delay have been reported, this manifestation is part of a broader phenotype where cognitive impairment is unlikely to represent a main feature. In the majority of cases, cognitive function is preserved.

Therefore, rating Amber on this panel. The phenotypes associated with LARS2 are better represented in other panels (e.g. Hearing loss) where this gene is already Green.; to: Comment on list classification: While a few cases with neurological symptoms including developmental delay or neurologic decline have been reported (PMID: 29205794; 30737337; 32442335), this manifestation is part of a broader phenotype where cognitive impairment is unlikely to represent the main feature. In the majority of cases, cognitive function is preserved.

Therefore, rating Amber on this panel. The phenotypes associated with LARS2 are better represented in other panels (e.g. Hearing loss) where this gene is already Green.
Intellectual disability v3.1006 LARS2 Arina Puzriakova Classified gene: LARS2 as Amber List (moderate evidence)
Intellectual disability v3.1006 LARS2 Arina Puzriakova Added comment: Comment on list classification: While are a few cases with neurological symptoms including developmental delay have been reported, this manifestation is part of a broader phenotype where cognitive impairment is unlikely to represent a main feature. In the majority of cases, cognitive function is preserved.

Therefore, rating Amber on this panel. The phenotypes associated with LARS2 are better represented in other panels (e.g. Hearing loss) where this gene is already Green.
Intellectual disability v3.1006 LARS2 Arina Puzriakova Gene: lars2 has been classified as Amber List (Moderate Evidence).
Rare anaemia v1.19 LARS2 Arina Puzriakova Mode of inheritance for gene: LARS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hearing loss v2.158 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from #615300: Perrault syndrome 4 to Perrault syndrome 4, OMIM:615300
Intellectual disability v3.1005 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from to Perrault syndrome 4, OMIM:615300; Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021; Leukodystrophy
Intellectual disability v3.1004 LARS2 Arina Puzriakova Mode of inheritance for gene: LARS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency v2.413 PRIM1 Arina Puzriakova Classified gene: PRIM1 as Amber List (moderate evidence)
Primary immunodeficiency v2.413 PRIM1 Arina Puzriakova Added comment: Comment on list classification: PRIM1 was added to this panel following discussion with Helen Brittain (Genomics England Clinical Team). It was agreed that there is sufficient evidence to rate this gene Green at the next review
Primary immunodeficiency v2.413 PRIM1 Arina Puzriakova Gene: prim1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency v2.412 PRIM1 Arina Puzriakova gene: PRIM1 was added
gene: PRIM1 was added to Primary immunodeficiency. Sources: Literature
Q2_21_rating tags were added to gene: PRIM1.
Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIM1 were set to 33060134
Phenotypes for gene: PRIM1 were set to Microcephalic primordial dwarfism, MONDO:0017950
Review for gene: PRIM1 was set to GREEN
Added comment: PRIM1 is currently not associated with any phenotype in OMIM (last edited in 2004) or Gene2Phenotype.

- PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature
Severe microcephaly v2.111 PRIM1 Arina Puzriakova edited their review of gene: PRIM1: Changed rating: GREEN
Severe microcephaly v2.111 PRIM1 Arina Puzriakova Classified gene: PRIM1 as Amber List (moderate evidence)
Severe microcephaly v2.111 PRIM1 Arina Puzriakova Added comment: Comment on list classification: Following discussion with Helen Brittain (Genomics England Clinical Team) it was agreed that there is sufficient evidence to rate this gene Green at the next review
Severe microcephaly v2.111 PRIM1 Arina Puzriakova Gene: prim1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.110 PRIM1 Arina Puzriakova Tag watchlist was removed from gene: PRIM1.
Tag Q2_21_rating tag was added to gene: PRIM1.
Laterality disorders and isomerism v1.27 NKX2-5 Ivone Leong Mode of inheritance for gene: NKX2-5 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Laterality disorders and isomerism v1.26 NKX2-5 Ivone Leong Publications for gene: NKX2-5 were set to
Laterality disorders and isomerism v1.25 CFAP52 Ivone Leong Tag Q2_21_rating tag was added to gene: CFAP52.
Laterality disorders and isomerism v1.25 CFAP52 Ivone Leong Classified gene: CFAP52 as Amber List (moderate evidence)
Laterality disorders and isomerism v1.25 CFAP52 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is enough evidence to support a gene-disease assocation. This gene should be rated Green at the next review.
Laterality disorders and isomerism v1.25 CFAP52 Ivone Leong Gene: cfap52 has been classified as Amber List (Moderate Evidence).
Laterality disorders and isomerism v1.24 CFAP52 Ivone Leong Phenotypes for gene: CFAP52 were changed from Heterotaxy to visceral heterotaxy, MONDO:0018677
Laterality disorders and isomerism v1.23 CFAP45 Ivone Leong Classified gene: CFAP45 as Amber List (moderate evidence)
Laterality disorders and isomerism v1.23 CFAP45 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with any phenotypes in OMIM or Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Laterality disorders and isomerism v1.23 CFAP45 Ivone Leong Gene: cfap45 has been classified as Amber List (Moderate Evidence).
Laterality disorders and isomerism v1.22 CFAP45 Ivone Leong Phenotypes for gene: CFAP45 were changed from Situs inversus; asthenospermia to Situs inversus, MONDO:0010029; male infertility due to sperm motility disorder, MONDO:0018395
Laterality disorders and isomerism v1.21 CFAP45 Ivone Leong Tag Q2_21_rating tag was added to gene: CFAP45.
Retinal disorders v2.177 AMACR Ivone Leong Classified gene: AMACR as Amber List (moderate evidence)
Retinal disorders v2.177 AMACR Ivone Leong Added comment: Comment on list classification: New gene added by Hannah Knight (Moorfields Eye Hospital). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Retinal disorders v2.177 AMACR Ivone Leong Gene: amacr has been classified as Amber List (Moderate Evidence).
Retinal disorders v2.176 AMACR Ivone Leong Tag Q2_21_rating tag was added to gene: AMACR.
Tag Q2_21_NHS_review tag was added to gene: AMACR.
Retinal disorders v2.176 AMACR Ivone Leong Phenotypes for gene: AMACR were changed from Retinitis pigmentosa to Retinitis pigmentosa, MONDO:0019200; Alpha-methylacyl-CoA racemase deficiency, OMIM:614307
Retinal disorders v2.175 AMACR Ivone Leong Publications for gene: AMACR were set to PMID: 21686617; 20821052; 11861706; 10655068; 15249642; 23286897
Intestinal failure v1.35 TMPRSS15 Ivone Leong Classified gene: TMPRSS15 as Amber List (moderate evidence)
Intestinal failure v1.35 TMPRSS15 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Intestinal failure v1.35 TMPRSS15 Ivone Leong Gene: tmprss15 has been classified as Amber List (Moderate Evidence).
Intestinal failure v1.34 TMPRSS15 Ivone Leong Tag Q2_21_rating tag was added to gene: TMPRSS15.
Intestinal failure v1.34 TMPRSS15 Ivone Leong Phenotypes for gene: TMPRSS15 were changed from Enterokinase deficiency, MIM# 226200 to Enterokinase deficiency, OMIM:226200
Intestinal failure v1.33 PLVAP Ivone Leong Classified gene: PLVAP as Amber List (moderate evidence)
Intestinal failure v1.33 PLVAP Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Intestinal failure v1.33 PLVAP Ivone Leong Gene: plvap has been classified as Amber List (Moderate Evidence).
Intestinal failure v1.32 PLVAP Ivone Leong Tag Q2_21_rating tag was added to gene: PLVAP.
Intestinal failure v1.32 PLVAP Ivone Leong Added comment: Comment on publications: PMID: 26207260. Patient is of Afgan descent born to consanguineous parents. Presented at 8 days of life with secretory diarrhea, metabolic acidosis, lethargy, poor feeding, and severe hyponatremia causing seizures. Further examination shows patient had bilateral colobomas, undescended testes, mildly dysplastic kidneys bilaterally, low-set ears, and micrognathia.

PMID: 29875123. 2 patients (first cousins) from a Muslim Arab consanguineous kindred presented with anasarca, severe hypoalbuminaemia and hypogammaglobinaemia.

PMID: 29661969. Patient is of Turkish descent born to consanguineous parents. Presented with severe haematochezia and moderate anasarca. Other findings: dysmorphism, metabolic acidosis, electrolyte deficiencies, elevated GGT, choroid plexus cysts, iris cysts, ASD, VSD, dilated megaureter with dilated renal pelvis, venous thrombosis.

PMID: 31215290. Patient born to consanguineous parents. As well as intestinal phenotypes, she also had dysmorphic features, renal and cardiac phenotypes.
Intestinal failure v1.32 PLVAP Ivone Leong Publications for gene: PLVAP were set to 29875123; 29661969; 26207260; 31215290
Intestinal failure v1.31 PLVAP Ivone Leong Phenotypes for gene: PLVAP were changed from Diarrhoea 10, protein-losing enteropathy type, MIM# 618183 to Diarrhoea 10, protein-losing enteropathy type, OMIM:618183
Intestinal failure v1.30 NEUROG3 Ivone Leong Classified gene: NEUROG3 as Amber List (moderate evidence)
Intestinal failure v1.30 NEUROG3 Ivone Leong Added comment: Comment on list classification: This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Intestinal failure v1.30 NEUROG3 Ivone Leong Gene: neurog3 has been classified as Amber List (Moderate Evidence).
Intestinal failure v1.29 NEUROG3 Ivone Leong Tag Q2_21_rating tag was added to gene: NEUROG3.
Intestinal failure v1.29 NEUROG3 Ivone Leong Phenotypes for gene: NEUROG3 were changed from Diarrhoea 4, malabsorptive, congenital, MIM# 610370 to Diarrhoea 4, malabsorptive, congenital, OMIM:610370
Structural eye disease v1.56 WNT2B Ivone Leong Classified gene: WNT2B as Amber List (moderate evidence)
Structural eye disease v1.56 WNT2B Ivone Leong Gene: wnt2b has been classified as Amber List (Moderate Evidence).
Structural eye disease v1.55 WNT2B Ivone Leong Publications for gene: WNT2B were set to
Structural eye disease v1.54 WNT2B Ivone Leong Phenotypes for gene: WNT2B were changed from 29909964; 33526876 to Diarrhoea 9, OMIM:618168; microcornea; coloboma, MONDO:0001476
Structural eye disease v1.53 WNT2B Ivone Leong edited their review of gene: WNT2B: Changed publications: 29909964, 33526876; Changed phenotypes: Diarrhoea 9, OMIM:618168, microcornea, coloboma, MONDO:0001476
Structural eye disease v1.53 WNT2B Ivone Leong gene: WNT2B was added
gene: WNT2B was added to Structural eye disease. Sources: Literature
watchlist tags were added to gene: WNT2B.
Mode of inheritance for gene: WNT2B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WNT2B were set to 29909964; 33526876
Review for gene: WNT2B was set to AMBER
Added comment: This gene is associated with a phenotype in OMIM but not Gene2Phenotype. This gene is also present on the Intestinal failure panel (Version 1.28).

Review submitted by Zornitza Stark on the Intestinal failure panel:
"Diarrhoea-9 is a form of neonatal-onset chronic diarrhoea characterized by an osmotic diarrhoea that is not substrate specific, abnormal crypt and villus architecture, and significant fat malabsorption. Three probands from two unrelated families and functional data suggesting severe intestinal dysregulation due to decreased intestinal stem cell number and function. Borderline Green/Amber. Sources: Expert Review
Zornitza Stark (Australian Genomics), 4 Jan 2021"

PMID: 33526876 reports an additional unrelated case. Patient is of Haitian descent (previous cases described in PMID:29909964 are of Vietnamese and Kuwaiti origins). Patient has neonatal onset diarrhoea with metabolic acidosis and failure to thrive. Patient also has bilateral microcornea and corneal clouding. Patient also presented with ambiguous genitalia and diagnosed with 46,XX testicular DSD. The authors reviewed the clinical findings of the previous patients they had reported on (PMID:29909964) and found that the Kuwaiti patients had bilateral microcornea, corneal neovascularization and thick corneas (I-2), and bilateral iridocorneal adhesions, congenital cataract, and iris coloboma (I-3). The gonadal findings in the Haitian patient was not seen in any of the other affected patients.

As there are only 2 cases of patients with microcornea and coloboma this gene has been given an Amber rating.
Sources: Literature
Disorders of sex development v2.46 WNT2B Ivone Leong gene: WNT2B was added
gene: WNT2B was added to Disorders of sex development. Sources: Literature
Mode of inheritance for gene: WNT2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT2B were set to 29909964; 33526876
Phenotypes for gene: WNT2B were set to Diarrhoea 9, OMIM:618168; 46,XX testicular disorder of sex development, MONDO:0100249
Review for gene: WNT2B was set to RED
Added comment: This gene is associated with a phenotype in OMIM but not Gene2Phenotype. This gene is also present on the Intestinal failure panel (Version 1.28).

Review submitted by Zornitza Stark on the Intestinal failure panel:
"Diarrhoea-9 is a form of neonatal-onset chronic diarrhoea characterized by an osmotic diarrhoea that is not substrate specific, abnormal crypt and villus architecture, and significant fat malabsorption. Three probands from two unrelated families and functional data suggesting severe intestinal dysregulation due to decreased intestinal stem cell number and function. Borderline Green/Amber. Sources: Expert Review
Zornitza Stark (Australian Genomics), 4 Jan 2021"

PMID: 33526876 reports an additional unrelated case. Patient is of Haitian descent (previous cases described in PMID:29909964 are of Vietnamese and Kuwaiti origins). Patient has neonatal onset diarrhoea with metabolic acidosis and failure to thrive. Patient also has bilateral microcornea and corneal clouding. Patient also presented with ambiguous genitalia and diagnosed with 46,XX testicular DSD. The authors reviewed the clinical findings of the previous patients they had reported on (PMID:29909964) and found that the Kuwaiti patients had bilateral microcornea, corneal neovascularization and thick corneas (I-2), and bilateral iridocorneal adhesions, congenital cataract, and iris coloboma (I-3). The gonadal findings in the Haitian patient was not seen in any of the other affected patients.

As there is only 1 case, this gene has been added as Red on this panel.
Sources: Literature
Intestinal failure v1.28 WNT2B Ivone Leong Classified gene: WNT2B as Amber List (moderate evidence)
Intestinal failure v1.28 WNT2B Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. This gene is associated with a relevant phenotype in OMIM and not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Intestinal failure v1.28 WNT2B Ivone Leong Gene: wnt2b has been classified as Amber List (Moderate Evidence).
Intestinal failure v1.27 WNT2B Ivone Leong Tag Q2_21_rating tag was added to gene: WNT2B.
Intestinal failure v1.27 WNT2B Ivone Leong Added comment: Comment on publications: PMID: 33526876 reports an additional unrelated case. Patient is of Haitian descent (previous cases described in PMID:29909964 are of Vietnamese and Kuwaiti origins). Patient has neonatal onset diarrhoea with metabolic acidosis and failure to thrive. Patient also has bilateral microcornea and corneal clouding. Patient also presented with ambiguous genitalia and diagnosed with 46,XX testicular DSD.

The authors reviewed the clinical findings of the previous patients they had reported on (PMID:29909964) and found that the Kuwaiti patients had bilateral microcornea, corneal neovascularization and thick corneas (I-2), and bilateral iridocorneal adhesions, congenital cataract, and iris coloboma (I-3). The gonadal findings in the Haitian patient was not seen in any of the other affected patients.
Intestinal failure v1.27 WNT2B Ivone Leong Publications for gene: WNT2B were set to 29909964
Intestinal failure v1.26 WNT2B Ivone Leong Phenotypes for gene: WNT2B were changed from Diarrhoea 9, MIM# 618168 to Diarrhoea 9, OMIM:618168
Intestinal failure v1.25 TTC37 Ivone Leong Phenotypes for gene: TTC37 were changed from Trichohepatoenteric syndrome 1 222470 to Trichohepatoenteric syndrome 1, OMM:222470
Intestinal failure v1.24 STXBP2 Ivone Leong Phenotypes for gene: STXBP2 were changed from Hemophagocytic lymphohistiocytosis, familial, 5 613101 to Hemophagocytic lymphohistiocytosis, familial, 5, OMIM:613101
Intestinal failure v1.23 STX3 Ivone Leong Phenotypes for gene: STX3 were changed from Microvillus inclusion disease; congenital diarrheal disorder to Microvillus inclusion disease, MONDO:0009635; diarrheal disorder, MONDO:0001673
Intestinal failure v1.22 SPINT2 Ivone Leong Phenotypes for gene: SPINT2 were changed from congenital sodium diarrhea; Congenital tufting enteropathy to Diarrhea 3, secretory sodium, congenital, syndromic, OMIM:270420
Intestinal failure v1.21 SLC9A3 Ivone Leong Phenotypes for gene: SLC9A3 were changed from Congenital sodium diarrhea to Diarrhea 8, secretory sodium, congenital, OMM:616868
Intestinal failure v1.20 SLC26A3 Ivone Leong Phenotypes for gene: SLC26A3 were changed from Congenital chloride diarrhea to Diarrhea 1, secretory chloride, congenital, OMIM:214700
Intestinal failure v1.19 SKIV2L Ivone Leong Added comment: Comment on publications: 27537055 - a pathogenic variant (heterozygous state) in this gene was reported in a patient using whole exome sequencing screening in 147 pediatric patients with monogenic Inflammatory Bowel Disease.
Intestinal failure v1.19 SKIV2L Ivone Leong Publications for gene: SKIV2L were set to 22444670; 27302973; 27537055 - a pathogenic variant (heterozygous state) in this gene was reported in a patient using whole exome sequencing screening in 147 pediatric patients with monogenic Inflammatory Bowel Disease.
Intestinal failure v1.18 SKIV2L Ivone Leong Phenotypes for gene: SKIV2L were changed from Trichohepatoenteric syndrome 2 614602 to Trichohepatoenteric syndrome 2, OMIM:614602
Intestinal failure v1.17 MYO5B Ivone Leong Phenotypes for gene: MYO5B were changed from Microvillus inclusion disease, 251850 to Microvillus inclusion disease, OMIM:251850
Intestinal failure v1.16 GUCY2C Ivone Leong Phenotypes for gene: GUCY2C were changed from Familial Diarrhea 6 614616 to Familial Diarrhea 6, OMIM:614616
Intestinal failure v1.15 GUCY2C Ivone Leong Phenotypes for gene: GUCY2C were changed from Familial Diarrhea 6 614616 to Familial Diarrhea 6 614616
Intestinal failure v1.14 EPCAM Ivone Leong Phenotypes for gene: EPCAM were changed from Diarrhea 5, with tufting enteropathy, congenital 613217 to Diarrhea 5, with tufting enteropathy, congenital, OMIM:613217
Intestinal failure v1.13 DGAT1 Ivone Leong Phenotypes for gene: DGAT1 were changed from Congenital diarrheal disorder to Congenital diarrheal disorder; ?Diarrhea 7, protein-losing enteropathy type, OMIM:615863
Pancreatitis v2.10 CELA3B Ivone Leong Classified gene: CELA3B as Amber List (moderate evidence)
Pancreatitis v2.10 CELA3B Ivone Leong Added comment: Comment on list classification: New gene added by Miranda Durkie. This gene is not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 31369399. Other affected members of this large family could not be tested and therefore the genetic status of the affected individuals are unknown. The family also has a variant in FOXN1, as the gene is not expressed in the pancreas the authors hypothesised that the FOXN1 variant was not causative.

PMID: 33565216. Four patients with p.Arg90Leu (c.269G>T) were from cases with familial chronic pancreatitis and young cases with idiopathic chronic pancreatitis (2 each). The familial chronic pancreatitis cases each have an affected first‐degree relative who have not been analysed yet.

This gene has been added as an Amber gene and will be reviewed by the GMS specialist group to see if there is enough evidence to promote to Green status.
Pancreatitis v2.10 CELA3B Ivone Leong Gene: cela3b has been classified as Amber List (Moderate Evidence).
Pancreatitis v2.9 CELA3B Ivone Leong Tag Q2_21_rating tag was added to gene: CELA3B.
Tag Q2_21_NHS_review tag was added to gene: CELA3B.
Pancreatitis v2.9 CELA3B Ivone Leong Phenotypes for gene: CELA3B were changed from Chronic Pancreatitis; Diabetes; Pancreatic cancer to Chronic Pancreatitis, MONDO:0005003; diabetes mellitus (disease), MONDO:0005015; Pancreatic cancer
Pancreatitis v2.8 CELA3B Ivone Leong Publications for gene: CELA3B were set to
Intellectual disability v3.1003 NCKAP1 Zornitza Stark reviewed gene: NCKAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33157009; Phenotypes: Intellectual disability, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v3.1003 LARS2 Zornitza Stark reviewed gene: LARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29205794, 32423379, 30737337, 26537577, 23541342; Phenotypes: Perrault syndrome 4, Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021, Leukodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1003 DPYS Zornitza Stark gene: DPYS was added
gene: DPYS was added to Intellectual disability. Sources: Expert Review
Mode of inheritance for gene: DPYS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DPYS were set to Dihydropyrimidinuria, MIM#222748
Review for gene: DPYS was set to GREEN
gene: DPYS was marked as current diagnostic
Added comment: Highly variable phenotype, but many have ID.
Sources: Expert Review
Intellectual disability v3.1003 DPM2 Zornitza Stark edited their review of gene: DPM2: Added comment: Further unrelated individual reported, main clinical features were truncal hypotonia, hypertonicity, congenital heart defects, intellectual disability, and generalized muscle wasting.; Changed rating: GREEN; Changed publications: 23109149, 33129689
Intellectual disability v3.1003 B4GALT1 Zornitza Stark reviewed gene: B4GALT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 11901181, 30653653, 21920538; Phenotypes: Congenital disorder of glycosylation, type Iid, MIM#607091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1003 AGO1 Zornitza Stark reviewed gene: AGO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30213762, 22495306, 23020937, 25363768, 25356899, 27620904, 29346770, 28135719; Phenotypes: Intellectual disability, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Primary immunodeficiency v2.411 ZNFX1 Boaz Palterer gene: ZNFX1 was added
gene: ZNFX1 was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: ZNFX1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZNFX1 were set to mendelian susceptibility to mycobacterial disease; MSMD; monocytosis.
Penetrance for gene: ZNFX1 were set to unknown
Review for gene: ZNFX1 was set to RED
Added comment: Le Voyer et al. described two patients from two unrelated kindreds with homozygous LOF variants in the ZNFX1 gene associated with mendelian susceptibility to mycobacterial disease (MSMD) and monocytosis. ( https://www.pnas.org/content/118/15/e2102804118 )
Sources: Literature
Primary immunodeficiency v2.411 SYK Boaz Palterer gene: SYK was added
gene: SYK was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: SYK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYK were set to 33782605
Phenotypes for gene: SYK were set to immunodeficiency; hypogammaglobulinemia; multi-organ inflammatory disease
Penetrance for gene: SYK were set to unknown
Mode of pathogenicity for gene: SYK 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: SYK was set to AMBER
Added comment: Wang et al. identified six patients from unrelated kindreds with monoallelic SYK variants causing immunodeficiency and a multiorgan inflammatory disease. The variants were proven to be functionally gain-of-function. Functional GOF was confirmed in knock-in mouse experiments.
Sources: Literature
Fetal anomalies v1.637 PLD1 Suzanne Drury gene: PLD1 was added
gene: PLD1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PLD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLD1 were set to 33645542
Phenotypes for gene: PLD1 were set to HP:0001654; HP:0001627; HP:0001638
Review for gene: PLD1 was set to GREEN
Added comment: PMID 33645542 identified 30 patients from 21 unrelated families of different ancestries with biallelic PLD1 variants. All 30 patients were diagnosed with severe congenital heart disease or
cardiomyopathy at the fetal or neonatal stage. PLD1 can also cause neonatal cardiomyopathy in the absence of congenital heart defects.
Sources: Literature
Dilated cardiomyopathy - adult and teen v1.13 RYR2 Matthew Edwards changed review comment from: On CGGL Royal Brompton DCM panel. Definitive ARVC/CPVT gene, appropriate for DCM panel due to possible phenotypic overlap. some evidence for exon 3 deletion specifically associated with DCM.; to: On CGGL Royal Brompton DCM panel. Definitive CPVT gene, appropriate for DCM panel due to possible phenotypic overlap as some evidence for exon 3 deletion specifically associated with DCM.
Ataxia and cerebellar anomalies - narrow panel v2.80 CLPP Sarah Leigh reviewed gene: CLPP: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v2.80 CLPP Sarah Leigh Publications for gene: CLPP were set to 25254289
Ataxia and cerebellar anomalies - narrow panel v2.79 CLPP Sarah Leigh Phenotypes for gene: CLPP were changed from Perrault syndrome 3 OMIM:614129; Perrault syndrome 3 MONDO:0013588 to Perrault syndrome 3 OMIM:614129; Perrault syndrome 3 MONDO:0013588
Congenital disorders of glycosylation v2.66 SSR4 Sarah Leigh commented on gene: SSR4: GlyGen link updated April 2021: https://www.glygen.org/protein/P51571-1#Disease
Congenital disorders of glycosylation v2.66 SLC39A8 Sarah Leigh commented on gene: SLC39A8: GlyGen link updated April 2021: https://www.glygen.org/protein/Q9C0K1-1#Disease
Congenital disorders of glycosylation v2.66 POMT2 Sarah Leigh commented on gene: POMT2: GlyGen link updated April 2021: https://www.glygen.org/protein/Q9UKY4-1#Disease
Congenital disorders of glycosylation v2.66 POMGNT1 Sarah Leigh commented on gene: POMGNT1: GlyGen link updated April 2021: https://www.glygen.org/protein/Q8WZA1-1#Disease
Congenital disorders of glycosylation v2.66 POMT1 Sarah Leigh commented on gene: POMT1: GlyGen link updated April 2021: https://www.glygen.org/protein/Q9Y6A1-1#Disease
Congenital disorders of glycosylation v2.66 PIGL Sarah Leigh commented on gene: PIGL: GlyGen link updated April 2021: https://www.glygen.org/protein/Q9Y2B2-1#Disease
Congenital disorders of glycosylation v2.66 PIGO Sarah Leigh commented on gene: PIGO: GlyGen link updated April 2021: https://www.glygen.org/protein/Q8TEQ8-1#Disease
Congenital disorders of glycosylation v2.66 PIGA Sarah Leigh commented on gene: PIGA: GlyGen link updated April 2021: https://www.glygen.org/protein/P37287-1#Disease
Congenital disorders of glycosylation v2.66 PGM1 Sarah Leigh commented on gene: PGM1: GlyGen link updated April 2021: https://www.glygen.org/protein/P36871-1#Disease
Congenital disorders of glycosylation v2.66 PGAP2 Sarah Leigh commented on gene: PGAP2: GlyGen link updated April 2021: https://www.glygen.org/protein/Q9UHJ9-1#Disease
Fetal anomalies v1.637 CLTC Suzanne Drury reviewed gene: CLTC: Rating: ; Mode of pathogenicity: None; Publications: PMID:33743358; Phenotypes: ; Mode of inheritance: None
Congenital disorders of glycosylation v2.66 LARGE1 Sarah Leigh commented on gene: LARGE1: GlyGen link updated April 2021: https://www.glygen.org/protein/O95461-1#Disease
Congenital disorders of glycosylation v2.66 FUT8 Sarah Leigh commented on gene: FUT8
Congenital disorders of glycosylation v2.66 FKTN Sarah Leigh commented on gene: FKTN: GlyGen link updated April 2021: https://www.glygen.org/protein/O75072-1#Disease
Congenital disorders of glycosylation v2.66 FKRP Sarah Leigh commented on gene: FKRP: GlyGen link updated April 2021: https://www.glygen.org/protein/Q9H9S5-1#Disease
Congenital disorders of glycosylation v2.66 EXT2 Sarah Leigh commented on gene: EXT2: GlyGen link updated April 2021: https://www.glygen.org/protein/Q93063-1#Disease
Congenital disorders of glycosylation v2.66 EXT1 Sarah Leigh changed review comment from: GlyGen link: https://www.glygen.org/protein/Q16394-1#Disease; to: GlyGen link updated April 2021: https://www.glygen.org/protein/Q16394-1#Disease
Congenital disorders of glycosylation v2.66 EXT1 Sarah Leigh changed review comment from: Comment on phenotypes: Also associated with Chondrosarcoma 215300 ; to: Comment on phenotypes: Also associated with Chondrosarcoma 215300
Congenital disorders of glycosylation v2.66 EXT1 Sarah Leigh commented on gene: EXT1: GlyGen link: https://www.glygen.org/protein/Q16394-1#Disease
Congenital disorders of glycosylation v2.66 DPAGT1 Sarah Leigh commented on gene: DPAGT1: GlyGen link updated April 2021: https://www.glygen.org/protein/Q9H3H5-1#Disease
Congenital disorders of glycosylation v2.66 CCDC115 Sarah Leigh commented on gene: CCDC115: GlyGen link updated April 2021: https://www.glygen.org/protein/Q96NT0-1#Disease
Congenital disorders of glycosylation v2.66 ATP6V0A2 Sarah Leigh commented on gene: ATP6V0A2: GlyGen link updated April 2021: https://www.glygen.org/protein/Q9Y487-1#Disease
Congenital disorders of glycosylation v2.66 TMEM165 Sarah Leigh commented on gene: TMEM165: GlyGen link updated April 2021: https://www.glygen.org/protein/Q9HC07-1#Disease
Ataxia and cerebellar anomalies - narrow panel v2.78 CLPP Sarah Leigh Classified gene: CLPP as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.78 CLPP Sarah Leigh Gene: clpp has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.77 CLPP Sarah Leigh Classified gene: CLPP as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.77 CLPP Sarah Leigh Gene: clpp has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.76 CLPP Sarah Leigh Publications for gene: CLPP were set to 25254289
Ataxia and cerebellar anomalies - narrow panel v2.75 CLPP Sarah Leigh Phenotypes for gene: CLPP were changed from Perrault syndrome 3, MIM# 614129 to Perrault syndrome 3 OMIM:614129; Perrault syndrome 3 MONDO:0013588
Undiagnosed metabolic disorders v1.450 CLN5 Sarah Leigh Phenotypes for gene: CLN5 were changed from Ceroid lipofuscinosis, neuronal, 5 256731 to Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745
Intellectual disability v3.1003 CLN5 Sarah Leigh Phenotypes for gene: CLN5 were changed from Ceroid lipofuscinosis, neuronal, 5, 256731; NEURONAL CEROID LIPOFUSCINOSIS TYPE 5 (CLN5) to Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745
Severe Paediatric Disorders v1.71 CLN5 Sarah Leigh Phenotypes for gene: CLN5 were changed from Ceroid lipofuscinosis, neuronal, 5, 256731 to Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745
Inborn errors of metabolism v2.106 CLN5 Sarah Leigh Phenotypes for gene: CLN5 were changed from Ceroid lipofuscinosis, neuronal, 5, 256731 to Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745
Retinal disorders v2.174 CLN5 Sarah Leigh Phenotypes for gene: CLN5 were changed from Eye Disorders; Ceroid lipofuscinosis, neuronal, 5, 256731 to Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745
Childhood onset dystonia or chorea or related movement disorder v1.86 CLN5 Sarah Leigh Phenotypes for gene: CLN5 were changed from Ceroid lipofuscinosis, neuronal, 5, 256731 to Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745
DDG2P v2.24 CLN5 Sarah Leigh Phenotypes for gene: CLN5 were changed from NEURONAL CEROID LIPOFUSCINOSIS TYPE 5 256731 to Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745
Ataxia and cerebellar anomalies - narrow panel v2.74 CLN5 Sarah Leigh edited their review of gene: CLN5: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least ten variants reported in at least nine unrelated cases.
Ataxia is a feature of Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745; Changed rating: GREEN
Ataxia and cerebellar anomalies - narrow panel v2.74 CLN5 Sarah Leigh Tag Q2_21_rating tag was added to gene: CLN5.
Ataxia and cerebellar anomalies - narrow panel v2.74 CLN5 Sarah Leigh Classified gene: CLN5 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.74 CLN5 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.74 CLN5 Sarah Leigh Gene: cln5 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.73 CLN5 Sarah Leigh Phenotypes for gene: CLN5 were changed from Ceroid lipofuscinosis, neuronal, 5, MIM# 256731 to Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745
Ataxia and cerebellar anomalies - narrow panel v2.72 BBS1 Sarah Leigh Tag Q2_21_rating tag was added to gene: BBS1.
Intellectual disability v3.1002 BBS1 Sarah Leigh Publications for gene: BBS1 were set to
Bardet Biedl syndrome v1.11 BBS1 Sarah Leigh Publications for gene: BBS1 were set to 12118255
Limb disorders v2.39 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from Polydactyly; Bardet-Biedl syndrome 1 209900 to Polydactyly; Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
Severe early-onset obesity v2.38 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from Obesity; Bardet-Biedl syndrome 1, OMIM:209900 to Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
Renal ciliopathies v1.41 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from Bardet Biedl syndrome 13; 268000; Bardet Biedl syndrome 1; Bardet Biedl syndrome 11 to Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
Intellectual disability v3.1001 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from Bardet-Biedl syndrome 1, 209900; BARDET-BIEDL SYNDROME TYPE 1 (BBS1) to Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
Retinal disorders v2.173 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from Eye Disorders; Retinitis pigmentosa; Bardet-Biedl syndrome 1, 209900 to Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
DDG2P v2.23 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from BARDET-BIEDL SYNDROME TYPE 1 209900 to Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
Fetal anomalies v1.637 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from BARDET-BIEDL SYNDROME TYPE 1 to Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
Unexplained paediatric onset end-stage renal disease v1.16 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from Ciliopathy genes associated with cystic kidney disease; Bardet-Biedl syndrome type 1 209900 to Ciliopathy genes associated with cystic kidney disease; Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
Skeletal dysplasia v2.87 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from Polydactyly; Bardet-Biedl syndrome 1 209900 to Polydactyly; Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
Bardet Biedl syndrome v1.10 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from Bardet-Biedl syndrome 1, 209900 to Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
Ataxia and cerebellar anomalies - narrow panel v2.72 BBS1 Sarah Leigh Phenotypes for gene: BBS1 were changed from Bardet-Biedl syndrome 1, MIM#209900 to Bardet-Biedl syndrome 1 OMIM:209900; Bardet-Biedl syndrome 1 MONDO:0008854
Ataxia and cerebellar anomalies - narrow panel v2.71 BBS1 Sarah Leigh edited their review of gene: BBS1: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in numerous unrelated cases.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.71 BBS1 Sarah Leigh Classified gene: BBS1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.71 BBS1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.71 BBS1 Sarah Leigh Gene: bbs1 has been classified as Amber List (Moderate Evidence).
Membranoproliferative glomerulonephritis v2.20 CFHR5 Sarah Leigh changed review comment from: PMID 22503529 reports a heterozygous 1bp insertion variant (rs565457964) in a child with Nephropathy due to CFHR5 deficiency OMIM:614809.; to: PMID 22503529 reports a heterozygous 1bp insertion variant (rs565457964) in a child with Nephropathy due to CFHR5 deficiency OMIM:614809 and persistent renal disease following a streptococcal infection. The variant was also seen in her unaffected mother and sister, which suggested that this variant is not sufficient to cause disease, but likely acts as a susceptibility factor for the development of glomerulonephritis.
Membranoproliferative glomerulonephritis v2.20 CFHR5 Sarah Leigh commented on gene: CFHR5
Membranoproliferative glomerulonephritis v2.20 CFHR5 Sarah Leigh Publications for gene: CFHR5 were set to 24172683; 20800271; 24067434; 23728178; 27458560; 21566112; 32928961
Membranoproliferative glomerulonephritis v2.19 CFHR5 Sarah Leigh Publications for gene: CFHR5 were set to 24172683; 20800271; 24067434; 23728178; 27458560; 21566112; 32928961]
Membranoproliferative glomerulonephritis v2.18 CFHR5 Sarah Leigh Publications for gene: CFHR5 were set to 24172683; 20800271; 24067434; 23728178; 27458560; 21566112
Membranoproliferative glomerulonephritis v2.17 CFHR5 Sarah Leigh Publications for gene: CFHR5 were set to 24172683; 20800271; 24067434; 23728178; 27458560
Additional findings health related - CNV analysis children v1.0 Eleanor Williams promoted panel to version 1.0
Additional findings health related - CNV analysis adult specific v1.0 Eleanor Williams promoted panel to version 1.0
Additional findings health related - children v1.0 Eleanor Williams promoted panel to version 1.0
Additional findings health related - adult specific v1.0 Eleanor Williams promoted panel to version 1.0
Gastrointestinal epithelial barrier disorders v1.60 ANO1 Arina Puzriakova Classified gene: ANO1 as Amber List (moderate evidence)
Gastrointestinal epithelial barrier disorders v1.60 ANO1 Arina Puzriakova Added comment: Comment on list classification: Rating Amber, awaiting further cases and review of phenotype associated with variants in this gene.
Gastrointestinal epithelial barrier disorders v1.60 ANO1 Arina Puzriakova Gene: ano1 has been classified as Amber List (Moderate Evidence).
Familial melanoma v1.9 POT1 Arina Puzriakova Phenotypes for gene: POT1 were changed from Melanoma, cutaneous malignant, susceptibility to, 10, 615848 to Melanoma, cutaneous malignant, susceptibility to, 10, OMIM:615848
Familial melanoma v1.8 POT1 Arina Puzriakova Publications for gene: POT1 were set to 24686849; 24686846; 29523635; 30451293; 30586141; 32325837
Familial melanoma v1.7 POT1 Arina Puzriakova edited their review of gene: POT1: Changed publications: 24686849, 24686846, 29523635, 30451293, 30586141, 32325837, 32907878
Additional findings reproductive carrier status v1.0 Eleanor Williams promoted panel to version 1.0
Ataxia and cerebellar anomalies - narrow panel v2.70 ATP8A2 Sarah Leigh edited their review of gene: ATP8A2: Added comment: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 21 variants reported in 17 unrelated cases with varying degrees of severity, together with supportive expression and functional studies (PMID 31612321).; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1000 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 27679995; 30012219; 29531481; 29531481; 31612321
Hereditary ataxia - adult onset v2.35 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 29531481; 30012219; 31612321
Ataxia and cerebellar anomalies - narrow panel v2.70 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 29531481; 30012219; 31612321; 27679995
Ataxia and cerebellar anomalies - narrow panel v2.69 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 29531481; 30012219; 31612321
Intellectual disability v3.999 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 27679995; 30012219; 29531481
Hereditary ataxia - adult onset v2.34 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 31612321; 30012219
Ataxia and cerebellar anomalies - narrow panel v2.68 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 30012219; 31612321
Ataxia and cerebellar anomalies - narrow panel v2.67 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 31612321
Hereditary ataxia - adult onset v2.33 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528; 31612321
Ataxia and cerebellar anomalies - narrow panel v2.66 ATP8A2 Sarah Leigh Tag Q2_21_rating tag was added to gene: ATP8A2.
Ataxia and cerebellar anomalies - narrow panel v2.66 ATP8A2 Sarah Leigh Classified gene: ATP8A2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.66 ATP8A2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.66 ATP8A2 Sarah Leigh Gene: atp8a2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.998 ATP8A2 Sarah Leigh Phenotypes for gene: ATP8A2 were changed from ?Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 615268; intellectual disability to ?Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 OMIM:615268; cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 MONDO:0014104
Ataxia and cerebellar anomalies - narrow panel v2.65 ATP8A2 Sarah Leigh Phenotypes for gene: ATP8A2 were changed from Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 615268 to ?Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 OMIM:615268; cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 MONDO:0014104
Hereditary ataxia - adult onset v2.32 ATP8A2 Sarah Leigh Phenotypes for gene: ATP8A2 were changed from Cerebellar ataxia, mental retardation and dysequilibirum syndrome 4 to ?Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 OMIM:615268; cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 MONDO:0014104
Hereditary ataxia - adult onset v2.31 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to 22892528
Ataxia and cerebellar anomalies - narrow panel v2.64 ATP8A2 Sarah Leigh Publications for gene: ATP8A2 were set to PMID: 22892528
Ataxia and cerebellar anomalies - narrow panel v2.63 ATCAY Sarah Leigh reviewed gene: ATCAY: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary ataxia v1.215 ATCAY Sarah Leigh reviewed gene: ATCAY: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v3.997 SPEN Arina Puzriakova Publications for gene: SPEN were set to 33057194
Intellectual disability v3.996 SPEN Arina Puzriakova Classified gene: SPEN as Amber List (moderate evidence)
Intellectual disability v3.996 SPEN Arina Puzriakova Added comment: Comment on list classification: There is now enough evidence to promote this gene to Green at the next review - sufficient cases (>20) with truncating SPEN variants and GDD/ID of relevant severity to this panel.
Intellectual disability v3.996 SPEN Arina Puzriakova Gene: spen has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.995 SPEN Arina Puzriakova Tag Q2_21_rating tag was added to gene: SPEN.
Childhood onset dystonia or chorea or related movement disorder v1.85 MED27 Arina Puzriakova Classified gene: MED27 as Amber List (moderate evidence)
Childhood onset dystonia or chorea or related movement disorder v1.85 MED27 Arina Puzriakova Gene: med27 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia or chorea or related movement disorder v1.84 MED27 Arina Puzriakova gene: MED27 was added
gene: MED27 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature
Q2_21_rating tags were added to gene: MED27.
Mode of inheritance for gene: MED27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED27 were set to 33443317
Phenotypes for gene: MED27 were set to Intellectual disability; Axial hypotonia; Spasticity; Dystonia; Cerebellar hypoplasia; Cataracts; Epilepsy
Review for gene: MED27 was set to GREEN
Added comment: MED27 is currently not associated with any phenotype in OMIM (last edited on 08/03/2012), but is listed in Gene2Phenotype with a 'probable' disease confidence rating for 'MED27-related neurodevelopmental disorder'

- PMID: 33443317 (2021) - 16 individuals from 11 families with a neurodevelopmental syndrome characterised by mild to profound GDD/ID (14/14), axial hypotonia (14/15), distal spasticity and dystonic movements (13/15), cerebellar hypoplasia (12/14), cataracts (10/15), epilepsy (9/15), and microcephaly (4/14). Exome sequencing revealed biallelic variants in the MED27 gene, including 3 recurrent variants found in 2 or more families with different background.

Overall sufficient (>3) unrelated cases for inclusion if phenotypes are considered to be within the scope of this panel - most individuals presented dystonic movements, but only 2 sibs experienced generalised dystonia.
Sources: Literature
Genetic epilepsy syndromes v2.315 MED27 Arina Puzriakova Classified gene: MED27 as Amber List (moderate evidence)
Genetic epilepsy syndromes v2.315 MED27 Arina Puzriakova Gene: med27 has been classified as Amber List (Moderate Evidence).
Genetic epilepsy syndromes v2.314 MED27 Arina Puzriakova gene: MED27 was added
gene: MED27 was added to Genetic epilepsy syndromes. Sources: Literature
Q2_21_rating tags were added to gene: MED27.
Mode of inheritance for gene: MED27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED27 were set to 33443317
Phenotypes for gene: MED27 were set to Intellectual disability; Axial hypotonia; Spasticity; Dystonia; Cerebellar hypoplasia; Cataracts; Epilepsy
Review for gene: MED27 was set to GREEN
Added comment: MED27 is currently not associated with any phenotype in OMIM (last edited on 08/03/2012), but is listed in Gene2Phenotype with a 'probable' disease confidence rating for 'MED27-related neurodevelopmental disorder'

- PMID: 33443317 (2021) - 16 individuals from 11 families with a neurodevelopmental syndrome characterised by mild to profound GDD/ID (14/14), axial hypotonia (14/15), distal spasticity and dystonic movements (13/15), cerebellar hypoplasia (12/14), cataracts (10/15), epilepsy (9/15), and microcephaly (4/14). Age of seizure onset ranged from 20 days to 5 years and seizure types were varied. Epilepsy was drug-resistant in 3/9 patients. Exome sequencing revealed biallelic variants in the MED27 gene, including 3 recurrent variants found in 2 or more families with different background.

Overall sufficient (>3) unrelated cases with epilepsy in patients with MED27 variants for inclusion on this panel as diagnostic-grade (Green).
Sources: Literature
Cataracts v2.68 MED27 Arina Puzriakova Classified gene: MED27 as Amber List (moderate evidence)
Cataracts v2.68 MED27 Arina Puzriakova Gene: med27 has been classified as Amber List (Moderate Evidence).
Cataracts v2.67 MED27 Arina Puzriakova gene: MED27 was added
gene: MED27 was added to Cataracts. Sources: Literature
Q2_21_rating tags were added to gene: MED27.
Mode of inheritance for gene: MED27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED27 were set to 33443317
Phenotypes for gene: MED27 were set to Intellectual disability; Axial hypotonia; Spasticity; Dystonia; Cerebellar hypoplasia; Cataracts; Epilepsy
Review for gene: MED27 was set to GREEN
Added comment: MED27 is currently not associated with any phenotype in OMIM (last edited on 08/03/2012), but is listed in Gene2Phenotype with a 'probable' disease confidence rating for 'MED27-related neurodevelopmental disorder'

- PMID: 33443317 (2021) - 16 individuals from 11 families with a neurodevelopmental syndrome characterised by mild to profound GDD/ID (14/14), axial hypotonia (14/15), distal spasticity and dystonic movements (13/15), cerebellar hypoplasia (12/14), epilepsy (9/15), and microcephaly (4/14). Cataracts were present in 10/15 patients, with four reporting mature cataracts, and 2 sibs had posterior cataracts. Exome sequencing revealed biallelic variants in the MED27 gene, including 3 recurrent variants found in 2 or more families with different background.

Overall sufficient (>3) unrelated cases with cataracts in patients in MED27 variants for inclusion on this panel as diagnostic-grade (Green).
Sources: Literature
Intellectual disability v3.995 MED27 Arina Puzriakova Phenotypes for gene: MED27 were changed from Intellectual disability; cerebellar hypoplasia; dystonia to Intellectual disability; Axial hypotonia; Spasticity; Dystonia; Cerebellar hypoplasia; Cataracts; Epilepsy
Intellectual disability v3.994 MED27 Arina Puzriakova Classified gene: MED27 as Amber List (moderate evidence)
Intellectual disability v3.994 MED27 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next review - at least 11 unrelated families reported with MED27 variants presenting overlapping phenotypes that include ID of relevant severity to this panel.
Intellectual disability v3.994 MED27 Arina Puzriakova Gene: med27 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.993 MED27 Arina Puzriakova Tag Q2_21_rating tag was added to gene: MED27.
Intellectual disability v3.993 MED27 Arina Puzriakova reviewed gene: MED27: Rating: GREEN; Mode of pathogenicity: None; Publications: 33443317; Phenotypes: Intellectual disability, Axial hypotonia, Spasticity, Dystonia, Cerebellar hypoplasia, Cataracts, Epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia - adult onset v2.30 ATCAY Sarah Leigh Publications for gene: ATCAY were set to 29449188; 14556008; 23226316
Hereditary ataxia v1.215 ATCAY Sarah Leigh Publications for gene: ATCAY were set to 29449188; 14556008; 23226316
Ataxia and cerebellar anomalies - narrow panel v2.63 ATCAY Sarah Leigh Publications for gene: ATCAY were set to 29449188; 14556008; 23226316
Hereditary ataxia - adult onset v2.29 ATCAY Sarah Leigh Phenotypes for gene: ATCAY were changed from Cerebellar Ataxia, Cayman type; Cayman Ataxia, 601238; Ataxia, cerebellar, Cayman type to Ataxia, cerebellar, Cayman type OMIM:601238; Cayman type cerebellar ataxia MONDO:0011025
Hereditary ataxia - adult onset v2.28 ATCAY Sarah Leigh Publications for gene: ATCAY were set to
Hereditary ataxia v1.214 ATCAY Sarah Leigh Publications for gene: ATCAY were set to
Ataxia and cerebellar anomalies - narrow panel v2.62 ATCAY Sarah Leigh Publications for gene: ATCAY were set to 29449188; 14556008
Hereditary ataxia v1.213 ATCAY Sarah Leigh Phenotypes for gene: ATCAY were changed from Ataxia, cerebellar, Cayman type ; Cerebellar Ataxia, Cayman type to Ataxia, cerebellar, Cayman type OMIM:601238; Cayman type cerebellar ataxia MONDO:0011025
Ataxia and cerebellar anomalies - narrow panel v2.61 ATCAY Sarah Leigh Phenotypes for gene: ATCAY were changed from Ataxia, cerebellar, Cayman type; Cerebellar Ataxia, Cayman type to Ataxia, cerebellar, Cayman type OMIM:601238; Cayman type cerebellar ataxia MONDO:0011025
Ataxia and cerebellar anomalies - narrow panel v2.60 ATCAY Sarah Leigh Publications for gene: ATCAY were set to
Severe microcephaly v2.110 EIF5A Arina Puzriakova Classified gene: EIF5A as Amber List (moderate evidence)
Severe microcephaly v2.110 EIF5A Arina Puzriakova Gene: eif5a has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.109 EIF5A Arina Puzriakova gene: EIF5A was added
gene: EIF5A was added to Severe microcephaly. Sources: Literature
Q2_21_rating tags were added to gene: EIF5A.
Mode of inheritance for gene: EIF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF5A were set to 33547280
Phenotypes for gene: EIF5A were set to Intellectual disability; microcephaly; dysmorphism
Review for gene: EIF5A was set to GREEN
Added comment: EIF5A is currently not associated with any phenotype in OMIM (last edited on 18/07/2019), but is listed in Gene2Phenotype with a 'probable' disease confidence rating for 'EIF5A-related craniofacial-neurodevelopmental disorder'

- PMID: 33547280 (2021) reports 7 unrelated individuals with different de novo heterozygous variants in the EIF5A gene. Microcephaly was evident at birth in 3/5 individuals, and assessments in later life indicated microcephaly in 5/7 cases (HC ranging between -1.94 and -7.47 SD). Other features include DD/ID and craniofacial dysmorphism, including micrognathia. Supportive functional data included.

Overall sufficient (>3) unrelated cases of microcephaly in patients with EIF5A variants, for inclusion on this panel.
Sources: Literature
Intellectual disability v3.993 EIF5A Arina Puzriakova Tag Q2_21_rating tag was added to gene: EIF5A.
Intellectual disability v3.993 EIF5A Arina Puzriakova Classified gene: EIF5A as Amber List (moderate evidence)
Intellectual disability v3.993 EIF5A Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene Green at the next review - PMID: 33547280 (2021) reports 7 unrelated individuals with different de novo heterozygous variants in the EIF5A gene. All were affected by variable degrees of DD and/or ID, mostly within the moderate severity range. Other features such as microcephaly and craniofacial dysmorphism were prominent but overall, the phenotype is best represented by this panel. Supportive functional data included.

EIF5A is currently not associated with any phenotype in OMIM (last edited on 18/07/2019), but is listed in Gene2Phenotype with a 'probable' disease confidence rating for 'EIF5A-related craniofacial-neurodevelopmental disorder'
Intellectual disability v3.993 EIF5A Arina Puzriakova Gene: eif5a has been classified as Amber List (Moderate Evidence).
Inherited bleeding disorders v1.159 ARPC1B Arina Puzriakova Phenotypes for gene: ARPC1B were changed from Platelet disorder; Thrombocytopenia and Immune Deficiency to Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, OMIM:617718; Combined immune deficiency with or without thrombocytopenia; Inflammatory predisposition
COVID-19 research v1.77 ARPC1B Arina Puzriakova Phenotypes for gene: ARPC1B were changed from inflammatory predisposition; Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, 617718; Mild thrombocytopenia with normal sized platelets, recurrent invasive infections, colitis, vasculitis, autoantibodies (ANA, ANCA), eosinophilia, defective Arp2/3, filament branching; Immunodeficiency with thrombocytopenia; Combined immunodeficiencies with associated or syndromic features; Thrombocytopenia & Immune Deficiency to Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, OMIM:617718; Combined immune deficiency with or without thrombocytopenia; Inflammatory predisposition
Severe Paediatric Disorders v1.70 ARPC1B Arina Puzriakova Phenotypes for gene: ARPC1B were changed from Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, 617718 to Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, OMIM:617718
Bleeding and platelet disorders v1.26 ARPC1B Arina Puzriakova Phenotypes for gene: ARPC1B were changed from 617718 Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease to Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, OMIM:617718
Cytopenia - NOT Fanconi anaemia v1.37 ARPC1B Arina Puzriakova Phenotypes for gene: ARPC1B were changed from Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, 617718 to Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, OMIM:617718
Primary immunodeficiency v2.411 ARPC1B Arina Puzriakova Publications for gene: ARPC1B were set to 28368018; 29127144; 27965109
Primary immunodeficiency v2.410 ARPC1B Arina Puzriakova Phenotypes for gene: ARPC1B were changed from Thrombocytopenia & Immune Deficiency; Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, 617718; inflammatory predisposition; Immunodeficiency with thrombocytopenia; Mild thrombocytopenia with normal sized platelets, recurrent invasive infections, colitis, vasculitis, autoantibodies (ANA, ANCA), eosinophilia, defective Arp2/3, filament branching; Combined immunodeficiencies with associated or syndromic features to Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, OMIM:617718; Combined immune deficiency with or without thrombocytopenia; Inflammatory predisposition
Primary immunodeficiency v2.409 MR1 Arina Puzriakova Classified gene: MR1 as Red List (low evidence)
Primary immunodeficiency v2.409 MR1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Boaz Palterer. Single patient described in PMID: 32709702 who presented immunodeficiency and a homozygous MR1 variant (c.92G>A, p.Arg31His) supported by some functional data. Rating Red, awaiting further evidence.
Primary immunodeficiency v2.409 MR1 Arina Puzriakova Gene: mr1 has been classified as Red List (Low Evidence).
Severe microcephaly v2.108 RAD50 Arina Puzriakova Phenotypes for gene: RAD50 were changed from Nijmegen breakage syndrome-like disorder, 613078 to Nijmegen breakage syndrome-like disorder, OMIM:613078
Severe microcephaly v2.107 RAD50 Arina Puzriakova Publications for gene: RAD50 were set to 1887849; 19409520; 32212377
Severe microcephaly v2.106 RAD50 Arina Puzriakova Classified gene: RAD50 as Amber List (moderate evidence)
Severe microcephaly v2.106 RAD50 Arina Puzriakova Added comment: Comment on list classification: There are now a total of 3 unrelated cases (PMIDs: 19409520; 32212377; 33378670) with a RAD50‐related syndrome including microcephaly. This therefore reaches the threshold for promotion of this gene to Green status at the next review (removed 'watchlist' tag and added 'Q2_21_rating' tag)
Severe microcephaly v2.106 RAD50 Arina Puzriakova Gene: rad50 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.105 RAD50 Arina Puzriakova Tag watchlist was removed from gene: RAD50.
Tag Q2_21_rating tag was added to gene: RAD50.
Severe microcephaly v2.105 RAD50 Arina Puzriakova edited their review of gene: RAD50: Added comment: - PMID: 33378670 (2020) - single patient described with bone marrow failure, immunodeficiency and developmental defects (including microcephaly), who was compound heterozygous for a frameshift and premature stop codon (c.2165dup; p.Glu723Glyfs∗5 - maternally inherited) and in-frame deletion (c.3109_3111del; p.Glu1035del - de novo) in the RAD50 gene.
Functional characterisation using patient-derived fibroblasts indicated defects in DNA replication, DNA repair, and DNA end resection; however, ATM-dependent DNA damage response remained intact. Studies in yeast modelling the variant corresponding to p.Glu1035del produced defects in both DNA repair and Tel1ATM-dependent signalling following thermal activation.; Changed rating: GREEN; Changed publications: 19409520, 32212377, 33378670; Changed phenotypes: Nijmegen breakage syndrome-like disorder, OMIM:613078; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.992 RAD50 Arina Puzriakova Phenotypes for gene: RAD50 were changed from Nijmegen breakage syndrome-like disorder, 613078 to Nijmegen breakage syndrome-like disorder, OMIM:613078
Intellectual disability v3.991 RAD50 Arina Puzriakova Publications for gene: RAD50 were set to 1887849; 19409520; 32212377
Intellectual disability v3.990 RAD50 Arina Puzriakova edited their review of gene: RAD50: Added comment: - PMID: 33378670 (2020) - single patient described with bone marrow failure, immunodeficiency and developmental defects, who was compound heterozygous for a frameshift and premature stop codon (c.2165dup; p.Glu723Glyfs∗5 - maternally inherited) and in-frame deletion (c.3109_3111del; p.Glu1035del - de novo) in the RAD50 gene.
Functional characterisation using patient-derived fibroblasts indicated defects in DNA replication, DNA repair, and DNA end resection; however, ATM-dependent DNA damage response remained intact. Studies in yeast modelling the variant corresponding to p.Glu1035del produced defects in both DNA repair and Tel1ATM-dependent signalling following thermal activation.

This is the third case published with biallelic variants in the RAD50 gene. Although authors report 'developmental defects', it is unclear whether this individual displayed cognitive impairment. Therefore, maintaining the Red gene rating on this panel.; Changed rating: RED; Changed publications: 19409520, 32212377, 33378670; Changed phenotypes: Nijmegen breakage syndrome-like disorder, OMIM:613078; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency v2.408 RAD50 Arina Puzriakova Phenotypes for gene: RAD50 were changed from bone marrow failure; immunodeficiency; developmental defect to Nijmegen breakage syndrome-like disorder, OMIM:613078; Bone marrow failure; Immunodeficiency
Primary immunodeficiency v2.407 RAD50 Arina Puzriakova Classified gene: RAD50 as Red List (low evidence)
Primary immunodeficiency v2.407 RAD50 Arina Puzriakova Added comment: Comment on list classification: New gene added by Boaz Palterer. Of the three total patients reported to date with biallelic variants in this gene, only one exhibited bone marrow failure and immunodeficiency (PMID: 33378670). Therefore rating Red on this panel until further cases are reported which indicate that RAD50 variants contribute to immunodeficiency
Primary immunodeficiency v2.407 RAD50 Arina Puzriakova Gene: rad50 has been classified as Red List (Low Evidence).
Neurotransmitter disorders v1.9 ALDH5A1 Sarah Leigh Classified gene: ALDH5A1 as Green List (high evidence)
Neurotransmitter disorders v1.9 ALDH5A1 Sarah Leigh Gene: aldh5a1 has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.59 ALDH5A1 Sarah Leigh edited their review of gene: ALDH5A1: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in numerous cases, together with supportive functional evidence and mouse model.; Changed rating: GREEN
Neurotransmitter disorders v1.8 ALDH5A1 Sarah Leigh edited their review of gene: ALDH5A1: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in numerous cases, together with supportive functional evidence and mouse model.; Changed rating: GREEN
Neurotransmitter disorders v1.8 ALDH5A1 Sarah Leigh Tag Q2_21_rating tag was added to gene: ALDH5A1.
Neurotransmitter disorders v1.8 ALDH5A1 Sarah Leigh Classified gene: ALDH5A1 as Amber List (moderate evidence)
Neurotransmitter disorders v1.8 ALDH5A1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Neurotransmitter disorders v1.8 ALDH5A1 Sarah Leigh Gene: aldh5a1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.59 ALDH5A1 Sarah Leigh Classified gene: ALDH5A1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.59 ALDH5A1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.59 ALDH5A1 Sarah Leigh Gene: aldh5a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.990 ALDH5A1 Sarah Leigh Publications for gene: ALDH5A1 were set to
Inborn errors of metabolism v2.105 ALDH5A1 Sarah Leigh Publications for gene: ALDH5A1 were set to 27604308
Genetic epilepsy syndromes v2.313 ALDH5A1 Sarah Leigh Publications for gene: ALDH5A1 were set to
Inborn errors of metabolism v2.104 ALDH5A1 Sarah Leigh Phenotypes for gene: ALDH5A1 were changed from Succinic semialdehyde dehydrogenase deficiency to Succinic semialdehyde dehydrogenase deficiency OMIM:271980; succinic semialdehyde dehydrogenase deficiency MONDO:0010083
Intellectual disability v3.989 ALDH5A1 Sarah Leigh Phenotypes for gene: ALDH5A1 were changed from Succinic semialdehyde dehydrogenase deficiency, 271980; SUCCINATE SEMIALDEHYDE DEHYDROGENASE DEFICIENCY to Succinic semialdehyde dehydrogenase deficiency OMIM:271980; succinic semialdehyde dehydrogenase deficiency MONDO:0010083
Genetic epilepsy syndromes v2.312 ALDH5A1 Sarah Leigh Phenotypes for gene: ALDH5A1 were changed from Succinic semialdehyde dehydrogenase deficiency 271980 to Succinic semialdehyde dehydrogenase deficiency OMIM:271980; succinic semialdehyde dehydrogenase deficiency MONDO:0010083
Neurotransmitter disorders v1.7 ALDH5A1 Sarah Leigh Phenotypes for gene: ALDH5A1 were changed from Succinic semialdehyde dehydrogenase deficiency, MIM# 271980 to Succinic semialdehyde dehydrogenase deficiency OMIM:271980; succinic semialdehyde dehydrogenase deficiency MONDO:0010083
Ataxia and cerebellar anomalies - narrow panel v2.58 ALDH5A1 Sarah Leigh Publications for gene: ALDH5A1 were set to 14635103
Intellectual disability v3.988 GNB1 Arina Puzriakova Phenotypes for gene: GNB1 were changed from Intellectual disability; developmental delay; Global developmental delay to Mental retardation, autosomal dominant 42, OMIM:616973
Intellectual disability v3.987 ADPRHL2 Sarah Leigh Phenotypes for gene: ADPRHL2 were changed from Developmental regression; Seizures; Ataxia; Intellectual disability to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170; neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures MONDO:0100095
Severe Paediatric Disorders v1.69 ADPRHL2 Sarah Leigh Phenotypes for gene: ADPRHL2 were changed from Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170; neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures MONDO:0100095 to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170; neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures MONDO:0100095
Severe Paediatric Disorders v1.68 ADPRHL2 Sarah Leigh Phenotypes for gene: ADPRHL2 were changed from Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, 618170 to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170; neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures MONDO:0100095
Hereditary ataxia - adult onset v2.27 ADPRHL2 Sarah Leigh Publications for gene: ADPRHL2 were set to
Intellectual disability v3.986 ADPRHL2 Sarah Leigh Publications for gene: ADPRHL2 were set to 30100084
Severe Paediatric Disorders v1.67 ADPRHL2 Sarah Leigh Publications for gene: ADPRHL2 were set to 30847515
Genetic epilepsy syndromes v2.311 ADPRHL2 Sarah Leigh Publications for gene: ADPRHL2 were set to 30100084
Genetic epilepsy syndromes v2.310 ADPRHL2 Sarah Leigh Phenotypes for gene: ADPRHL2 were changed from Intellectual disability, cerebellar atrophy, ataxia and epilepsy to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170; neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures MONDO:0100095
DDG2P v2.22 ADPRHL2 Sarah Leigh Added comment: Comment on phenotypes: Degenerative Pediatric Stress Induced Epileptic Ataxia Syndrome;Neurodegeneration with Developmental Delay Ataxia and Axonal Neuropathy
DDG2P v2.22 ADPRHL2 Sarah Leigh Phenotypes for gene: ADPRHL2 were changed from Degenerative Pediatric Stress Induced Epileptic Ataxia Syndrome; Neurodegeneration with Developmental Delay Ataxia and Axonal Neuropathy to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170; neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures MONDO:0100095
Ataxia and cerebellar anomalies - narrow panel v2.57 ADPRHL2 Sarah Leigh Classified gene: ADPRHL2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.57 ADPRHL2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Ataxia and cerebellar anomalies - narrow panel v2.57 ADPRHL2 Sarah Leigh Gene: adprhl2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.56 ADPRHL2 Sarah Leigh edited their review of gene: ADPRHL2: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 8 variants reported in 8 unrelated cases, together with supportive fuctional studies and a Drosophila paralog where a loss of Parg resulted in lethality on oxidative challenge that was rescued by human ADPRHL2.; Changed rating: GREEN
Primary immunodeficiency v2.406 RAD50 Arina Puzriakova reviewed gene: RAD50: Rating: RED; Mode of pathogenicity: None; Publications: 33378670; Phenotypes: Nijmegen breakage syndrome-like disorder, OMIM:613078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism v1.32 SPRY4 Ivone Leong Publications for gene: SPRY4 were set to 23643382
Ataxia and cerebellar anomalies - narrow panel v2.56 ADPRHL2 Sarah Leigh commented on gene: ADPRHL2
Hypogonadotropic hypogonadism v1.31 SPRY4 Ivone Leong Tag Q2_21_expert_review tag was added to gene: SPRY4.
Hypogonadotropic hypogonadism v1.31 SPRY4 Ivone Leong Classified gene: SPRY4 as Amber List (moderate evidence)
Hypogonadotropic hypogonadism v1.31 SPRY4 Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber.

PMID:23643382 - 14 unrelated cases had variants in SPRY4, 3 cases had variants in other genes (DUSP6 and FGFR1).

PMID: 32389901 - 1 cases had variants in SPRY4 and PLXNA1.

Based on the available evidence, this variants in this gene may contribute to disease. Therefore this gene has been promoted from Red to Amber.
Hypogonadotropic hypogonadism v1.31 SPRY4 Ivone Leong Gene: spry4 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.56 ADPRHL2 Sarah Leigh Tag new-gene-name tag was added to gene: ADPRHL2.
Ataxia and cerebellar anomalies - narrow panel v2.56 ADPRHL2 Sarah Leigh Phenotypes for gene: ADPRHL2 were changed from Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170 to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170; neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures MONDO:0100095
Hereditary ataxia - adult onset v2.26 ADPRHL2 Sarah Leigh Phenotypes for gene: ADPRHL2 were changed from Neurodegeneration, childhood-onset, stress-induced with variable ataxia and seizures, 618170 to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170; neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures MONDO:0100095
Ataxia and cerebellar anomalies - narrow panel v2.55 ADPRHL2 Sarah Leigh Phenotypes for gene: ADPRHL2 were changed from Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM#618170 to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures OMIM:618170
Hypogonadotropic hypogonadism v1.30 SPRY4 Ivone Leong Phenotypes for gene: SPRY4 were changed from Hypogonadotropic hypogonadism 17 with or without anosmia 615266 to Hypogonadotropic hypogonadism 17 with or without anosmia, OMIM:615266
Hypogonadotropic hypogonadism idiopathic v1.42 IL17RD Ivone Leong edited their review of gene: IL17RD: Added comment: In addition to the review by Zornitza Stark (Australian Genomics), PMID: 23643382 states the following:

"Collectively, these data indicate that IL17RD mutations are strongly associated with KS and hearing loss; however, one allelic defect is most likely not sufficient, meaning that additional affected alleles in the same and/or other genes must be present to create the phenotype of KS with hearing loss."; Changed rating: AMBER
Hypogonadotropic hypogonadism idiopathic v1.42 IL17RD Ivone Leong Tag Q2_21_expert_review tag was added to gene: IL17RD.
Hypogonadotropic hypogonadism idiopathic v1.42 DUSP6 Ivone Leong Classified gene: DUSP6 as Amber List (moderate evidence)
Hypogonadotropic hypogonadism idiopathic v1.42 DUSP6 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype.

PMID: 23643382 - 5 cases with variants in DUSP6 (3 of these cases have variants in other genes FGFR1 and SPRY4).

PMID: 32389901 - 6 cases with variants in DUSP6 (1 case also has variants in CCDC141).

Based on the available evidence this gene has been given an Amber rating and will be reviewed by the GMS specialist group.
Hypogonadotropic hypogonadism idiopathic v1.42 DUSP6 Ivone Leong Gene: dusp6 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism idiopathic v1.41 DUSP6 Ivone Leong Tag Q2_21_expert_review tag was added to gene: DUSP6.
Hypogonadotropic hypogonadism idiopathic v1.41 FGF17 Ivone Leong Classified gene: FGF17 as Amber List (moderate evidence)
Hypogonadotropic hypogonadism idiopathic v1.41 FGF17 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype.

PMID: 23643382 identfied 3 cases with variants in the FGF17 gene. However, 1 of these cases have variants in other genes as well (FLRT3, HS6ST1 and FGFR1).

Based on the available evidence variants in this gene contribute to disease with variable penetrance. This gene has been given an Amber rating until further evidence is available.
Hypogonadotropic hypogonadism idiopathic v1.41 FGF17 Ivone Leong Gene: fgf17 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism idiopathic v1.40 FGF17 Ivone Leong Tag Q2_21_expert_review tag was added to gene: FGF17.
Skeletal dysplasia v2.86 SCUBE3 Sarah Leigh Phenotypes for gene: SCUBE3 were changed from to Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies OMIM:619184
Skeletal dysplasia v2.85 SCUBE3 Sarah Leigh edited their review of gene: SCUBE3: Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 5 variants reported in 5 unrelated cases, together with supportive functional and mouse model studies (PMID 33308444).; Changed rating: GREEN
Skeletal dysplasia v2.85 SCUBE3 Sarah Leigh Classified gene: SCUBE3 as Amber List (moderate evidence)
Skeletal dysplasia v2.85 SCUBE3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Skeletal dysplasia v2.85 SCUBE3 Sarah Leigh Gene: scube3 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.84 SCUBE3 Sarah Leigh Tag Q2_21_rating tag was added to gene: SCUBE3.
Skeletal dysplasia v2.84 SCUBE3 Sarah Leigh Publications for gene: SCUBE3 were set to
Primary immunodeficiency v2.406 POU2AF1 Arina Puzriakova Classified gene: POU2AF1 as Red List (low evidence)
Primary immunodeficiency v2.406 POU2AF1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Boaz Palterer. Single patient described in PMID: 33571536 with agammaglobulinemia and a homozygous POU2AF1 variant (c.233delC, p.Thr78Lysfs∗63) supported by functional data. Rating Red, awaiting further evidence.
Primary immunodeficiency v2.406 POU2AF1 Arina Puzriakova Gene: pou2af1 has been classified as Red List (Low Evidence).
Primary immunodeficiency v2.405 GIMAP5 Arina Puzriakova Tag treatable tag was added to gene: GIMAP5.
Tag watchlist tag was added to gene: GIMAP5.
Primary immunodeficiency v2.405 GIMAP5 Arina Puzriakova Classified gene: GIMAP5 as Amber List (moderate evidence)
Primary immunodeficiency v2.405 GIMAP5 Arina Puzriakova Added comment: Comment on list classification: New gene added by Boaz Palterer. 4 unrelated families with an immunodeficiency disorder and difference biallelic LoF variants in the GIMAP5 gene. Clinical improvement in Gimap5-deficient mice and a human patient was observed following treatment with rapamycin (mTORC1 inhibitor)

Although there are sufficient cases with a relevant phenotype, rating this gene Amber while pending publication of the Park 2021 article, as information can change from the initial bioRxiv upload to peer-reviewed publication. Added 'watchlist' tag and will re-curate when the paper is published.
Primary immunodeficiency v2.405 GIMAP5 Arina Puzriakova Gene: gimap5 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency v2.404 MAP1LC3B2 Arina Puzriakova Classified gene: MAP1LC3B2 as Red List (low evidence)
Primary immunodeficiency v2.404 MAP1LC3B2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Boaz Palterer. Single patient described in PMID:33310865 with recurrent herpes simplex virus 2-induced lymphocytic Mollaret's meningitis, and a MAP1LC3B2 variant (c.325C>A) supported by functional data. Rating Red, awaiting further evidence.
Primary immunodeficiency v2.404 MAP1LC3B2 Arina Puzriakova Gene: map1lc3b2 has been classified as Red List (Low Evidence).
Primary immunodeficiency v2.403 ATG4A Arina Puzriakova Classified gene: ATG4A as Red List (low evidence)
Primary immunodeficiency v2.403 ATG4A Arina Puzriakova Added comment: Comment on list classification: New gene added by Boaz Palterer. Single patient described in PMID:33310865 with recurrent herpes simplex virus 2-induced lymphocytic Mollaret's meningitis, and a ATG4A variant (c.268C>A) supported by functional data. Rating Red, awaiting further evidence.
Primary immunodeficiency v2.403 ATG4A Arina Puzriakova Gene: atg4a has been classified as Red List (Low Evidence).
Bleeding and platelet disorders v1.25 MAST2 Arina Puzriakova Classified gene: MAST2 as Red List (low evidence)
Bleeding and platelet disorders v1.25 MAST2 Arina Puzriakova Added comment: Comment on list classification: Rating Red as only a single family reported at this time (PMID:33465109)
Bleeding and platelet disorders v1.25 MAST2 Arina Puzriakova Gene: mast2 has been classified as Red List (Low Evidence).
Bleeding and platelet disorders v1.24 MAST2 Arina Puzriakova Phenotypes for gene: MAST2 were changed from Thrombophilia; venous thrombosis to Venous thromboembolism; Thrombophilia
Thrombophilia v1.19 MAST2 Arina Puzriakova gene: MAST2 was added
gene: MAST2 was added to Thrombophilia. Sources: Literature
Mode of inheritance for gene: MAST2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAST2 were set to 33465109
Phenotypes for gene: MAST2 were set to Venous thromboembolism; Thrombophilia
Review for gene: MAST2 was set to RED
Added comment: - PMID: 33465109 (2021) - Single missense variant (p.Arg89Gln) identified in a French family with venous thrombosis and thrombophilia. Missense variant reviewed by in silico tools only. MAST2 knockdown was shown to affect regulation of TFP1 and SERPINE1 gene expression, known to regulate the haemostatic properties of endothelial cells. RNAi of MAST2 followed by RNAseq also showed expression changes in many other downstream targets.
Sources: Literature
Cytopenia - NOT Fanconi anaemia v1.36 RPL27 Arina Puzriakova commented on gene: RPL27
Cytopenia - NOT Fanconi anaemia v1.36 RPL27 Arina Puzriakova Tag Q2_21_expert_review tag was added to gene: RPL27.
Severe microcephaly v2.105 PRIM1 Arina Puzriakova gene: PRIM1 was added
gene: PRIM1 was added to Severe microcephaly. Sources: Literature
watchlist tags were added to gene: PRIM1.
Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIM1 were set to 33060134
Phenotypes for gene: PRIM1 were set to Microcephalic primordial dwarfism, MONDO:0017950
Review for gene: PRIM1 was set to AMBER
Added comment: PRIM1 is currently not associated with any phenotype in OMIM (last edited in 2004) or Gene2Phenotype.

- PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature
Retinal disorders v2.172 AMACR Hannah Knight gene: AMACR was added
gene: AMACR was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: AMACR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMACR were set to PMID: 21686617; 20821052; 11861706; 10655068; 15249642; 23286897
Phenotypes for gene: AMACR were set to Retinitis pigmentosa
Penetrance for gene: AMACR were set to Complete
Mode of pathogenicity for gene: AMACR was set to Other
Review for gene: AMACR was set to GREEN
Added comment: Only three reported mutations to our knowledge:
c.154T>C; p.Ser52Pro (most common)
c.367G>A; p.Asp123Asn
c.559G>A; p.Gly187Arg

For some patients, the retinal disorder can be the first manifestation of the condition, prior to developing neurological symptoms. We believe this gene should be on the retinal disorders panel to enable a quicker diagnosis and pre-emptive referrals to neurology.
Sources: Literature
Autism v0.22 TMPRSS9 Arina Puzriakova Phenotypes for gene: TMPRSS9 were changed from autism spectrum disorder to Progressive intellectual and neurological deterioration; Global developmental delay; Intellectual disability; Autism; Epilepsy
Autism v0.21 TMPRSS9 Arina Puzriakova Classified gene: TMPRSS9 as Red List (low evidence)
Autism v0.21 TMPRSS9 Arina Puzriakova Added comment: Comment on list classification: Rating this gene Red as second case is based on unpublished results. Also added to ID panel.
Autism v0.21 TMPRSS9 Arina Puzriakova Gene: tmprss9 has been classified as Red List (Low Evidence).
Autism v0.20 TMPRSS9 Arina Puzriakova reviewed gene: TMPRSS9: Rating: ; Mode of pathogenicity: None; Publications: 31943016; Phenotypes: Progressive intellectual and neurological deterioration, Global developmental delay, Intellectual disability, Autism, Epilepsy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.985 TMPRSS9 Arina Puzriakova Added comment: Comment on mode of inheritance: Rating this gene Red as second case is based on unpublished results, but with a watchlist tag as new data on this gene-disease association may become available soon.
Intellectual disability v3.985 TMPRSS9 Arina Puzriakova Mode of inheritance for gene: TMPRSS9 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.984 TMPRSS9 Arina Puzriakova gene: TMPRSS9 was added
gene: TMPRSS9 was added to Intellectual disability. Sources: Other
watchlist tags were added to gene: TMPRSS9.
Mode of inheritance for gene: TMPRSS9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMPRSS9 were set to 31943016
Phenotypes for gene: TMPRSS9 were set to Progressive intellectual and neurological deterioration; Global developmental delay; Intellectual disability; Autism; Epilepsy
Review for gene: TMPRSS9 was set to RED
Added comment: TMPRSS9 is currently not associated with any phenotype in OMIM or Gene2Phenotype.

- PMID: 31943016 (2020) - Single female subject with compound heterozygous nonsense variants (paternal: c.286C>T, p.R96*; maternal: c.1267C>T; p.R423*) in TMPRSS9. Early childhood development was normal until 2.5 years of age when she experienced profound developmental regression, including speech, social interaction and motor skills, resulting in ASD and profound ID. Knockout mice showed decreased social interest and recognition, and additionally borderline recognition memory deficit in aged female mice.

- Conference poster (Genomics of Rare Disease 2021) - 'ZOEMBA: combining metabolomics and genomics data to solve the unsolved' by Oud et al, United for Metabolic Diseases (UMD), Netherlands -
Trio WES revealed compound heterozygous variants (paternal: c.143-1G>A, p.?; maternal: c.1864G>A; p.V622M) in the TMPRSS9 gene in a female proband with GDD, PIND, aggression, autism and epilepsy. The individual was recruited on the basis of 'suspicion of an inherited metabolic disorder and extensive genetic and metabolic work-up with no diagnosis'.
Sources: Other
Intellectual disability v3.983 DDB1 Arina Puzriakova Classified gene: DDB1 as Amber List (moderate evidence)
Intellectual disability v3.983 DDB1 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to promote this gene to Green at the next review - sufficient unrelated cases (8) presenting consistent features primarily characterised by ID/DD and hypotonia, supported by functional data (PMID:33743206)
Intellectual disability v3.983 DDB1 Arina Puzriakova Gene: ddb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v3.982 DDB1 Arina Puzriakova changed review comment from: - PMID: 33743206 (2021) - 8 unrelated individuals with de novo variants in DDB1, including one recurrent variant in four individuals (c.637G>A, p.Glu213Lys) and two different substitutions at the same amino acid residue (p.Arg188Trp and p.Arg188Gln). Clinical features were consistent and include hypotonia (7/8) and mild-moderate developmental delay or intellectual disability (8/8) and similar facial gestalt. Brachydactyly was common and most noticeable in the feet (6/8), and two individuals had cutaneous toe syndactyly. All three older individuals had a BMI in the obese range for their age. Functional studies using patient-derived lymphoblasts showed altered DDB1 function resulting in abnormal DNA damage signatures and histone methylation following UV-induced DNA damage.
Sources: Literature; to: - PMID: 33743206 (2021) - 8 unrelated individuals with de novo variants in DDB1, including one recurrent variant in four individuals (c.637G>A, p.Glu213Lys) and two different substitutions at the same amino acid residue (p.Arg188Trp and p.Arg188Gln). Clinical features were consistent and include hypotonia (7/8) and mild-moderate developmental delay or intellectual disability (8/8) and similar facial gestalt. Brachydactyly was common and most noticeable in the feet (6/8), and two individuals had cutaneous toe syndactyly. All three older individuals had a BMI in the obese range for their age. Functional studies using patient-derived lymphoblasts showed altered DDB1 function resulting in abnormal DNA damage signatures and histone methylation following UV-induced DNA damage.

Variants in other CRL4 complex components, such as CUL4B (MIM# 300304) and PHIP (MIM# 612870), have been shown to cause overlapping phenotypes consisting of syndromic ID with hypotonia and obesity.
Sources: Literature
Intellectual disability v3.982 DDB1 Arina Puzriakova Tag Q2_21_rating tag was added to gene: DDB1.
Intellectual disability v3.982 DDB1 Arina Puzriakova gene: DDB1 was added
gene: DDB1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: DDB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DDB1 were set to 33743206
Phenotypes for gene: DDB1 were set to Intellectual disability
Review for gene: DDB1 was set to GREEN
Added comment: - PMID: 33743206 (2021) - 8 unrelated individuals with de novo variants in DDB1, including one recurrent variant in four individuals (c.637G>A, p.Glu213Lys) and two different substitutions at the same amino acid residue (p.Arg188Trp and p.Arg188Gln). Clinical features were consistent and include hypotonia (7/8) and mild-moderate developmental delay or intellectual disability (8/8) and similar facial gestalt. Brachydactyly was common and most noticeable in the feet (6/8), and two individuals had cutaneous toe syndactyly. All three older individuals had a BMI in the obese range for their age. Functional studies using patient-derived lymphoblasts showed altered DDB1 function resulting in abnormal DNA damage signatures and histone methylation following UV-induced DNA damage.
Sources: Literature
Intellectual disability v3.981 GSPT2 Arina Puzriakova Tag watchlist tag was added to gene: GSPT2.
Intellectual disability v3.981 GSPT2 Arina Puzriakova commented on gene: GSPT2
Genetic epilepsy syndromes v2.309 NEUROD2 Arina Puzriakova Publications for gene: NEUROD2 were set to 30323019; 16504944
Genetic epilepsy syndromes v2.308 NEUROD2 Arina Puzriakova edited their review of gene: NEUROD2: Changed publications: 16504944, 30323019, 33438828
Genetic epilepsy syndromes v2.308 NEUROD2 Arina Puzriakova reviewed gene: NEUROD2: Rating: ; Mode of pathogenicity: None; Publications: 30323019, 16504944; Phenotypes: Developmental and epileptic encephalopathy 72, OMIM:618374; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Genetic epilepsy syndromes v2.308 NEUROD2 Arina Puzriakova Phenotypes for gene: NEUROD2 were changed from Epileptic encephalopathy, early infantile, 72, MIM# 618374 to Developmental and epileptic encephalopathy 72, OMIM:618374
Adult onset movement disorder v1.113 YY1 Arina Puzriakova Phenotypes for gene: YY1 were changed from Gabriele-de Vries syndrome to Gabriele-de Vries syndrome, OMIM:617557
Adult onset movement disorder v1.112 VAMP2 Arina Puzriakova Publications for gene: VAMP2 were set to
Adult onset movement disorder v1.111 VAMP2 Arina Puzriakova Mode of inheritance for gene: VAMP2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset movement disorder v1.110 VAMP2 Arina Puzriakova Phenotypes for gene: VAMP2 were changed from to Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements, OMIM:618760
Adult onset movement disorder v1.109 UCHL1 Arina Puzriakova Phenotypes for gene: UCHL1 were changed from ?{Parkinson disease 5, susceptibility to}; ?{Parkinson disease 5, susceptibility to}, 613643; Spastic paraplegia 79, autosomal recessive, 615491 to {?Parkinson disease 5, susceptibility to}, OMIM:613643
Adult onset movement disorder v1.108 TAF1 Arina Puzriakova Phenotypes for gene: TAF1 were changed from Dystonia-Parkinsonism, X-linked, 314250; SVA retrotransposon insertion Dystonia-Parkinsonism, X-linked, 314250; (NB complex mutation) to Dystonia-Parkinsonism, X-linked, OMIM:314250
Adult onset movement disorder v1.107 PDE2A Arina Puzriakova Phenotypes for gene: PDE2A were changed from to Intellectual developmental disorder with paroxysmal dyskinesia or seizures, OMIM:619150
Adult onset movement disorder v1.106 PDE2A Arina Puzriakova Mode of inheritance for gene: PDE2A was changed from to BIALLELIC, autosomal or pseudoautosomal
Adult onset movement disorder v1.105 CHCHD2 Arina Puzriakova Phenotypes for gene: CHCHD2 were changed from 616710; Parkinson disease 22, autosomal dominant to Parkinson disease 22, autosomal dominant, OMIM:616710
Adult onset movement disorder v1.104 AUH Arina Puzriakova Phenotypes for gene: AUH were changed from 3-methylglutaconic aciduria, type I, 250950; Dystonia to 3-methylglutaconic aciduria, type I, OMIM:250950; Dystonia
Adult onset movement disorder v1.103 ARX Arina Puzriakova Phenotypes for gene: ARX were changed from Partington Syndrome, OMIM:300382 to Partington Syndrome, OMIM:309510
Adult onset movement disorder v1.102 ARX Arina Puzriakova Phenotypes for gene: ARX were changed from Partington Syndrome, 300382; Dystonia to Partington Syndrome, OMIM:300382
Adult onset movement disorder v1.101 ARSA Arina Puzriakova Mode of inheritance for gene: ARSA was changed from to BIALLELIC, autosomal or pseudoautosomal
Adult onset movement disorder v1.100 ARSA Arina Puzriakova Phenotypes for gene: ARSA were changed from Metachromatic leukodystrophy, 250100; Dystonia to Metachromatic leukodystrophy, OMIM:250100
Adult onset movement disorder v1.99 XPR1 Arina Puzriakova Phenotypes for gene: XPR1 were changed from Basal ganglia calcification, idiopathic, 6 616413 to Basal ganglia calcification, idiopathic, 6, OMIM:616413
Adult onset movement disorder v1.98 WDR45 Arina Puzriakova Phenotypes for gene: WDR45 were changed from Neurodegeneration with brain iron accumulation 5 300894; Dystonia; beta-propeller protein-associated neurodegeneration to Neurodegeneration with brain iron accumulation 5, OMIM:300894
Adult onset movement disorder v1.97 VPS35 Arina Puzriakova Phenotypes for gene: VPS35 were changed from PARK17; PARKINSON DISEASE 17; Parkinson disease 17, 614203; Parkinson Disease, Dominant; late onset parkinson disease to Parkinson disease 17, OMIM:614203
Adult onset movement disorder v1.96 VPS13A Arina Puzriakova Phenotypes for gene: VPS13A were changed from complex parkinsonism; Choreoacanthocytosis 200150 to Choreoacanthocytosis, OMIM:200150
Adult onset movement disorder v1.95 TUBB4A Arina Puzriakova Added comment: Comment on phenotypes: This gene is also associated with Leukodystrophy, hypomyelinating, 6, OMIM:612438
Adult onset movement disorder v1.95 TUBB4A Arina Puzriakova Phenotypes for gene: TUBB4A were changed from Complex parkinsonism; hypomyelinating leukodystrophy 6; ?Dystonia 4, torsion, autosomal dominant, 128101; Dystonia; hereditary whispering dysphonia to Dystonia 4, torsion, autosomal dominant, OMIM:128101
Adult onset movement disorder v1.94 TIMM8A Arina Puzriakova Publications for gene: TIMM8A were set to 22736418
Adult onset movement disorder v1.93 TIMM8A Arina Puzriakova Phenotypes for gene: TIMM8A were changed from Mohr-Tranebjaerg syndrome, 304700; Deafness-Dystonia-Optic Neuronopathy Syndrome to Mohr-Tranebjaerg syndrome, OMIM:304700
Adult onset movement disorder v1.92 THAP1 Arina Puzriakova Phenotypes for gene: THAP1 were changed from Dystonia 6, torsion, 602629; Dystonia to Dystonia 6, torsion, OMIM:602629
Adult onset movement disorder v1.91 TBK1 Arina Puzriakova Phenotypes for gene: TBK1 were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 4, 616439 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 4, OMIM:616439
Adult onset movement disorder v1.90 SYNJ1 Arina Puzriakova Phenotypes for gene: SYNJ1 were changed from juvenile Parkinsonism; Early Onset Complex Disease; Parkinson disease 20, early-onset, 615530; Parkinson disease 20, early-onset to Parkinson disease 20, early-onset, OMIM:615530
Adult onset movement disorder v1.89 SPR Arina Puzriakova Publications for gene: SPR were set to http://www.ncbi.nlm.nih.gov/books/NBK1155/; 22522443
Adult onset movement disorder v1.88 SPR Arina Puzriakova Phenotypes for gene: SPR were changed from Dystonia, dopa-responsive, due to sepiapterin reductase deficiency 612716; Dopa-Responsive Dystonia; paediatric form of dopa responsive dystonia; Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716 to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716
Adult onset movement disorder v1.87 SPG11 Arina Puzriakova Phenotypes for gene: SPG11 were changed from Complex parkinsonism; hereditary spastic paraparesis; Early Onset Complex Disease; early onset parkinsonism, levo dopa responsve to Spastic paraplegia 11, autosomal recessive, OMIM:604360; Charcot-Marie-Tooth disease, axonal, type 2X, OMIM:616668; Amyotrophic lateral sclerosis 5, juvenile, OMIM:602099
Hypogonadotropic hypogonadism idiopathic v1.40 IL17RD Ivone Leong reviewed gene: IL17RD: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism idiopathic v1.40 IL17RD Ivone Leong Tag Q2_21_MOI tag was added to gene: IL17RD.
Hypogonadotropic hypogonadism idiopathic v1.40 IL17RD Ivone Leong Phenotypes for gene: IL17RD were changed from Hypogonadotropic hypogonadism type 18 (OMIM 615267) to Hypogonadotropic hypogonadism 18 with or without anosmia, OMIM:615267
Adult onset movement disorder v1.86 SNCA Arina Puzriakova Phenotypes for gene: SNCA were changed from Autosomal dominant Parkinson's disease with alpha-synuclein rearrangements (PARK1/4); Dementia, Lewy body, 127750; Parkinson disease 4, 605543; Parkinson disease 1, 168601 to Dementia, Lewy body, OMIM:127750; Parkinson disease 4, OMIM:605543; Parkinson disease 1, OMIM:168601
Hypogonadotropic hypogonadism idiopathic v1.39 IL17RD Ivone Leong Publications for gene: IL17RD were set to
Adult onset movement disorder v1.85 SLC30A10 Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease; hypermanganesemia with dystonia-1 (HMNDYT1), increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, Brain MRI shows hyperintensities in the basal ganglia to Hypermanganesemia with dystonia 1, OMIM:613280
Adult onset movement disorder v1.84 SLC2A1 Arina Puzriakova Added comment: Comment on phenotypes: This gene is also associated with Stomatin-deficient cryohydrocytosis with neurologic defects, OMIM:608885 and {Epilepsy, idiopathic generalized, susceptibility to, 12}, OMIM:614847
Adult onset movement disorder v1.84 SLC2A1 Arina Puzriakova Phenotypes for gene: SLC2A1 were changed from EPILEPSY, IDIOPATHIC GENERALIZED; dystonia 9; GLUT1 deficiency syndrome 2; GLUT1 deficiency syndrome 1; GLUT1 deficiency syndrome 2, childhood onset; Dystonia; GLUT1 deficiency syndrome 1, infantile onset, severe; GLUT1 DEFICIENCY SYNDROME 1; GLUT1 deficiency syndrome 1, 606777; paroxysmal exertion-induced dyskinesia with or without epilepsy and/or hemolytic anemia to Dystonia 9, OMIM:601042; GLUT1 deficiency syndrome 1, infantile onset, severe, OMIM:606777; GLUT1 deficiency syndrome 2, childhood onset, OMIM:612126
Adult onset movement disorder v1.83 SLC20A2 Arina Puzriakova Phenotypes for gene: SLC20A2 were changed from Basal ganglia calcification, idiopathic, 1 213600 to Basal ganglia calcification, idiopathic, 1, OMIM:213600
Adult onset movement disorder v1.82 SLC19A3 Arina Puzriakova Phenotypes for gene: SLC19A3 were changed from Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) 607483 to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), OMIM:607483
Adult onset movement disorder v1.81 SGCE Arina Puzriakova Phenotypes for gene: SGCE were changed from Myoclonus dystonia syndrome; Myoclonus-Dystonia; maternally imprinted Dystonia-11, myoclonic, 159900 to Dystonia-11, myoclonic, OMIM:159900
Adult onset movement disorder v1.80 RNF216 Arina Puzriakova Phenotypes for gene: RNF216 were changed from Cerebellar ataxia and hypogonadotropic hypogonadism, 212840 to Cerebellar ataxia and hypogonadotropic hypogonadism, OMIM:212840
Adult onset movement disorder v1.79 RAB39B Arina Puzriakova Added comment: Comment on phenotypes: This gene is also associated with Mental retardation, X-linked 72, OMIM:300271
Adult onset movement disorder v1.79 RAB39B Arina Puzriakova Phenotypes for gene: RAB39B were changed from Waisman syndrome 311510; early-onset parkinsonism and intellectual disability to Waisman syndrome, OMIM:311510
Adult onset movement disorder v1.78 PRRT2 Arina Puzriakova Added comment: Comment on phenotypes: This gene is also associated with Seizures, benign familial infantile, 2, OMIM:605751
Adult onset movement disorder v1.78 PRRT2 Arina Puzriakova Phenotypes for gene: PRRT2 were changed from SEIZURES, BENIGN FAMILIAL INFANTILE, 2; episodic kinesigenic dyskinesia; EPISODIC KINESIGENIC DYSKINESIA 1; dystonia and occasionally hemiplegic migraine and epilepsy; CONVULSIONS, FAMILIAL INFANTILE, WITH PAROXYSMAL CHOREOATHETOSIS to Episodic kinesigenic dyskinesia 1, OMIM:128200; Convulsions, familial infantile, with paroxysmal choreoathetosis, OMIM:602066
Adult onset movement disorder v1.77 PRNP Arina Puzriakova Added comment: Comment on phenotypes: This gene is also associated with {Kuru, susceptibility to}, OMIM:245300; Insomnia, fatal familial, OMIM:600072; Spongiform encephalopathy with neuropsychiatric features, OMIM:606688
Adult onset movement disorder v1.77 PRNP Arina Puzriakova Phenotypes for gene: PRNP were changed from Cerebral amyloid angiopathy, PRNP-related 137440; Huntington disease-like 1 603218; Gerstmann-Straussler disease 137440; Creutzfeldt-Jakob disease 123400 to Cerebral amyloid angiopathy, PRNP-related, OMIM:137440; Huntington disease-like 1, OMIM:603218; Gerstmann-Straussler disease, OMIM:137440; Creutzfeldt-Jakob disease, OMIM:123400
Adult onset movement disorder v1.76 PRKRA Arina Puzriakova Publications for gene: PRKRA were set to 24142417; 22842711; 26990861; 25142429; 18420150 - a novel heterozygous variant c.266_267delAT; PMID: 26990861 - c.665C>T homozygous variant was identified in 3 affected siblings with Early-Onset Generalized Dystonia-Parkinsonism (and was heterozygous in the unaffected patients and an unaffected sibling). It was confirmed by Sanger sequencing and had a frequency of 0.01% in the Exome Aggregation Consortium database, predicted to be deleterious by 2 of 6 in silico tools. They showed it was within a founder haplotype shared by all previoulsy reported cases. The Authors state Screening of PRKRA is warranted in all patients with early-onset generalized dystonia, or dystonia parkinsonism compatible with autosomal recessive inheritance; p.H89fsX20 was reported in a proband with early childhood-onset leg dystonia (though testing in the parents was not mentioned).; 25737287; 25737287 Compound het variants (c.G230C (p.Cys77Ser), and in exon 7, c.G638T (p.Cys213Phe)) identified in the two affected siblings reported with dystonia without parkinsonism, unaffected family members were heterozygous; 25142429 In a Polish family, the homozygous p.Pro222Leu mutation segregated with autosomal-recessive, early-onset generalized dystonia and slight parkinsonism; 18420150; 18243799 - two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. A region of homozygosity was found in all affected individuals, and narrowed down to the homozygous variant c.665C>T (P222L); 22842711 describes the clinical features of three original cases with homozygous PRKRA variants - the patients presented with either a pure generalised dystonia or with a dystonia-parkinsonism that was relatively unresponsive to L-dopa; http://www.ncbi.nlm.nih.gov/books/NBK1155/; 24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, and c.637T>C (p.C213R) was a novel mutation; 18243799; 25914261
Adult onset movement disorder v1.75 PRKRA Arina Puzriakova changed review comment from: - PMID: 18420150 - a novel heterozygous variant c.266_267delAT identified in a patient with generalised dystonia

- PMID: 26990861 - c.665C>T homozygous variant was identified in 3 affected siblings with Early-Onset Generalized Dystonia-Parkinsonism (and was heterozygous in the unaffected patients and an unaffected sibling). It was confirmed by Sanger sequencing and had a frequency of 0.01% in the Exome Aggregation Consortium database, predicted to be deleterious by 2 of 6 in silico tools. They showed it was within a founder haplotype shared by all previously reported cases. The authors state screening of PRKRA is warranted in all patients with early-onset generalized dystonia, or dystonia parkinsonism compatible with autosomal recessive inheritance

- PMID: 25737287 Compound het variants (c.G230C (p.Cys77Ser), and in exon 7, c.G638T (p.Cys213Phe)) identified in the two affected siblings reported with dystonia without parkinsonism, unaffected family members were heterozygous
25142429 In a Polish family, the homozygous p.Pro222Leu mutation segregated with autosomal-recessive, early-onset generalized dystonia and slight parkinsonism

- PMID: 18243799 - two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. A region of homozygosity was found in all affected individuals, and narrowed down to the homozygous variant c.665C>T (P222L)

- PMID: 22842711 - describes the clinical features of three original cases with homozygous PRKRA variants - the patients presented with either a pure generalised dystonia or with a dystonia-parkinsonism that was relatively unresponsive to L-dopa

- PMID: 24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, and c.637T>C (p.C213R) was a novel mutation; to: Copied and removed from publications field:

- PMID: 18420150 - a novel heterozygous variant c.266_267delAT identified in a patient with generalised dystonia

- PMID: 26990861 - c.665C>T homozygous variant was identified in 3 affected siblings with Early-Onset Generalized Dystonia-Parkinsonism (and was heterozygous in the unaffected patients and an unaffected sibling). It was confirmed by Sanger sequencing and had a frequency of 0.01% in the Exome Aggregation Consortium database, predicted to be deleterious by 2 of 6 in silico tools. They showed it was within a founder haplotype shared by all previously reported cases. The authors state screening of PRKRA is warranted in all patients with early-onset generalized dystonia, or dystonia parkinsonism compatible with autosomal recessive inheritance

- PMID: 25737287 Compound het variants (c.G230C (p.Cys77Ser), and in exon 7, c.G638T (p.Cys213Phe)) identified in the two affected siblings reported with dystonia without parkinsonism, unaffected family members were heterozygous
25142429 In a Polish family, the homozygous p.Pro222Leu mutation segregated with autosomal-recessive, early-onset generalized dystonia and slight parkinsonism

- PMID: 18243799 - two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. A region of homozygosity was found in all affected individuals, and narrowed down to the homozygous variant c.665C>T (P222L)

- PMID: 22842711 - describes the clinical features of three original cases with homozygous PRKRA variants - the patients presented with either a pure generalised dystonia or with a dystonia-parkinsonism that was relatively unresponsive to L-dopa

- PMID: 24142417 - Compound heterozygous variants were reported in a patient with early onset dystonia c.665C>T (p.P222L) inherited from his mother, and c.637T>C (p.C213R) was a novel mutation
Adult onset movement disorder v1.75 PRKRA Arina Puzriakova commented on gene: PRKRA
Adult onset movement disorder v1.75 PRKRA Arina Puzriakova Phenotypes for gene: PRKRA were changed from Early-Onset Generalized Dystonia-Parkinsonism; Early Onset Complex Disease; Dystonia 16; early-Onset Generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa; early-onset generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa; Dystonia; Dystonia 16, 612067 to Dystonia 16, OMIM:612067
Adult onset movement disorder v1.74 PRKN Arina Puzriakova Publications for gene: PRKN were set to PMID: 22956510
Adult onset movement disorder v1.73 PRKN Arina Puzriakova Phenotypes for gene: PRKN were changed from Parkinson Disease, Juvenile; juvenile parkinsonism/dystonia; Dystonia; Parkinson disease, juvenile, type 2; Parkinson Disease 2, Autosomal Recessive Juvenile to Parkinson disease, juvenile, type 2, OMIM:600116
Adult onset movement disorder v1.72 PNKD Arina Puzriakova Phenotypes for gene: PNKD were changed from Familial Paroxysmal Nonkinesigenic Dyskinesia; PAROXYSMAL NONKINESIGENIC DYSKINESIA 1; Paroxysmal nonkinesigenic dyskinesia, 118800 to Paroxysmal nonkinesigenic dyskinesia 1, OMIM:118800
Adult onset movement disorder v1.71 PLA2G6 Arina Puzriakova Publications for gene: PLA2G6 were set to 18799783; 18570303; 16783378
Neurodegenerative disorders - adult onset v2.174 PLA2G6 Arina Puzriakova Phenotypes for gene: PLA2G6 were changed from Infantile neuroaxonal dystrophy 1, OMIM:256600; Neurodegeneration with brain iron accumulation 2B, OMIM:610217; Parkinson disease 14, OMIM:612953 to Parkinson disease 14, autosomal recessive, OMIM:612953; Neurodegeneration with brain iron accumulation 2B, OMIM:610217
Adult onset movement disorder v1.70 PLA2G6 Arina Puzriakova Phenotypes for gene: PLA2G6 were changed from PLA2G6-associated neurodegeneration; Parkinson disease 14, autosomal recessive 612953; Neurodegeneration with brain iron accumulation 2B 610217; Infantile neuroaxonal dystrophy 1 256600 to Parkinson disease 14, autosomal recessive, OMIM:612953; Neurodegeneration with brain iron accumulation 2B, OMIM:610217
Adult onset movement disorder v1.69 PINK1 Arina Puzriakova Publications for gene: PINK1 were set to
Adult onset movement disorder v1.68 PINK1 Arina Puzriakova Phenotypes for gene: PINK1 were changed from Parkinson Disease 6, Autosomal Recessive Early-Onset; Parkinson disease 6, early onset, 605909; Dystonia to Parkinson disease 6, early onset, OMIM:605909
Adult onset movement disorder v1.67 PDGFRB Arina Puzriakova Phenotypes for gene: PDGFRB were changed from Basal ganglia calcification, idiopathic, 4 615007 to Basal ganglia calcification, idiopathic, 4, OMIM:615007
Hypogonadotropic hypogonadism idiopathic v1.38 DUSP6 Ivone Leong Phenotypes for gene: DUSP6 were changed from Hypogonadotropic hypogonadism 19 with or without anosmia, MIM# 615269 to Hypogonadotropic hypogonadism 19 with or without anosmia, OMIM:615269
Hypogonadotropic hypogonadism idiopathic v1.37 LEPR Ivone Leong Tag Q2_21_rating tag was added to gene: LEPR.
Hypogonadotropic hypogonadism idiopathic v1.37 LEPR Ivone Leong Classified gene: LEPR as Amber List (moderate evidence)
Hypogonadotropic hypogonadism idiopathic v1.37 LEPR Ivone Leong Added comment: Comment on list classification: This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Hypogonadotropic hypogonadism idiopathic v1.37 LEPR Ivone Leong Gene: lepr has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism idiopathic v1.36 LEPR Ivone Leong Phenotypes for gene: LEPR were changed from Obesity, morbid, due to leptin receptor deficiency (MIM#614963) to Obesity, morbid, due to leptin receptor deficiency, OMIM:614963
Hypogonadotropic hypogonadism idiopathic v1.35 LEP Ivone Leong Classified gene: LEP as Amber List (moderate evidence)
Hypogonadotropic hypogonadism idiopathic v1.35 LEP Ivone Leong Added comment: Comment on list classification: This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Hypogonadotropic hypogonadism idiopathic v1.35 LEP Ivone Leong Gene: lep has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism idiopathic v1.34 LEP Ivone Leong Tag Q2_21_rating tag was added to gene: LEP.
Adult onset movement disorder v1.66 PDGFB Arina Puzriakova Publications for gene: PDGFB were set to 26129893
Adult onset movement disorder v1.65 PDGFB Arina Puzriakova Phenotypes for gene: PDGFB were changed from Basal ganglia calcification, idiopathic, 5 615483 to Basal ganglia calcification, idiopathic, 5, OMIM:615483
Adult onset movement disorder v1.64 PDE10A Arina Puzriakova Publications for gene: PDE10A were set to 27058446; 27058447; 28949041; 29130591; 30345538
Hypogonadotropic hypogonadism idiopathic v1.34 LEP Ivone Leong Phenotypes for gene: LEP were changed from Obesity, morbid, due to leptin deficiency (MIM#614962) to Obesity, morbid, due to leptin deficiency, OMIM:614962
Adult onset movement disorder v1.63 PDE10A Arina Puzriakova Publications for gene: PDE10A were set to 27058447; 27058446
Hypogonadotropic hypogonadism idiopathic v1.33 GNRH1 Ivone Leong commented on gene: GNRH1
Hypogonadotropic hypogonadism idiopathic v1.33 GNRH1 Ivone Leong Tag Q2_21_rating tag was added to gene: GNRH1.
Adult onset movement disorder v1.62 PDE10A Arina Puzriakova Phenotypes for gene: PDE10A were changed from Striatal degeneration, autosomal dominant 616922; Dyskinesia, limb and orofacial, infantile-onset 616921 to Striatal degeneration, autosomal dominant, OMIM:616922; Dyskinesia, limb and orofacial, infantile-onset, OMIM:616921
Adult onset movement disorder v1.61 PDE10A Arina Puzriakova Tag Q2_21_rating tag was added to gene: PDE10A.
Adult onset movement disorder v1.61 PDE10A Arina Puzriakova commented on gene: PDE10A
Hypogonadotropic hypogonadism idiopathic v1.33 GNRH1 Ivone Leong Phenotypes for gene: GNRH1 were changed from Hypogonadotropic hypogonadism 12 with or without anosmia, OMIM:614841 to ?Hypogonadotropic hypogonadism 12 with or without anosmia, OMIM:614841
Hypogonadotropic hypogonadism idiopathic v1.32 GNRH1 Ivone Leong Phenotypes for gene: GNRH1 were changed from Hypogonadotropic hypogonadism type 12 (OMIM 614841) to Hypogonadotropic hypogonadism 12 with or without anosmia, OMIM:614841
Hypogonadotropic hypogonadism idiopathic v1.31 GNRH1 Ivone Leong Publications for gene: GNRH1 were set to
Neurodegenerative disorders - adult onset v2.173 VPS13C Ivone Leong Phenotypes for gene: VPS13C were changed from Parkinson disease 23, autosomal recessive, early onset; 616840 to Parkinson disease 23, autosomal recessive, early onset, OMIM:616840
Neurodegenerative disorders - adult onset v2.172 TUBB4A Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Leukodystrophy, hypomyelinating, 6 612438;?Dystonia 4, torsion, autosomal dominant, 128101;hypomyelinating leukodystrophy 6;Implicated autosomal dominant variants in two families with ataxia;Dystonia;Torsion dystonia 4 (128101) - some individuals with ataxia;ataxia;hereditary whispering dysphonia;Complex parkinsonism;hypomyelinating leukodystrophy 6 (612438) - ataxia reported.;Dystonia 4, torsion, autosomal dominant 128101
Neurodegenerative disorders - adult onset v2.172 TUBB4A Ivone Leong Phenotypes for gene: TUBB4A were changed from Leukodystrophy, hypomyelinating, 6 612438; ?Dystonia 4, torsion, autosomal dominant, 128101; hypomyelinating leukodystrophy 6; Implicated autosomal dominant variants in two families with ataxia; Dystonia; Torsion dystonia 4 (128101) - some individuals with ataxia; ataxia; hereditary whispering dysphonia; Complex parkinsonism; hypomyelinating leukodystrophy 6 (612438) - ataxia reported.; Dystonia 4, torsion, autosomal dominant 128101 to Leukodystrophy, hypomyelinating, 6, OMIM:612438; Dystonia 4, torsion, autosomal dominant, OMIM:128101
Neurodegenerative disorders - adult onset v2.171 TUBA4A Ivone Leong Phenotypes for gene: TUBA4A were changed from Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, 616208 to Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, OMIM:616208
Neurodegenerative disorders - adult onset v2.170 TAF1 Ivone Leong Phenotypes for gene: TAF1 were changed from Dystonia-Parkinsonism, X-linked, 314250 to Dystonia-Parkinsonism, X-linked, OMIM:314250
Neurodegenerative disorders - adult onset v2.169 TAF1 Ivone Leong Phenotypes for gene: TAF1 were changed from SVA retrotransposon insertion Dystonia-Parkinsonism, X-linked, 314250; (NB complex mutation); Dystonia-Parkinsonism, X-linked, 314250 to Dystonia-Parkinsonism, X-linked, 314250
Neurodegenerative disorders - adult onset v2.168 SS18L1 Ivone Leong Phenotypes for gene: SS18L1 were changed from Amyotrophic lateral sclerosis 105400 to Amyotrophic lateral sclerosis, MONDO:0004976
Neurodegenerative disorders - adult onset v2.167 SS18L1 Ivone Leong Publications for gene: SS18L1 were set to 23708140; 24360741
Neurodegenerative disorders - adult onset v2.166 SNCB Ivone Leong Phenotypes for gene: SNCB were changed from Dementia, Lewy body, 127750 to Dementia, Lewy body, OMIM:127750
Neurodegenerative disorders - adult onset v2.165 SLC30A10 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
hypermanganesemia with dystonia-1 (HMNDYT1), increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, Brain MRI shows hyperintensities in the basal ganglia;Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, andChronic Liver Disease;Hypermanganesemia with dystonia, polycythemia, and cirrhosis, 613280;Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease
Neurodegenerative disorders - adult onset v2.165 SLC30A10 Ivone Leong Phenotypes for gene: SLC30A10 were changed from hypermanganesemia with dystonia-1 (HMNDYT1), increased serum manganese, motor neurodegeneration with extrapyramidal features, polycythemia, and hepatic dysfunction, Brain MRI shows hyperintensities in the basal ganglia; Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, andChronic Liver Disease; Hypermanganesemia with dystonia, polycythemia, and cirrhosis, 613280; Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease to Hypermanganesemia with dystonia 1, OMIM:613280
Adult onset movement disorder v1.61 PDE10A Arina Puzriakova Tag Q2_21_MOI tag was added to gene: PDE10A.
Neurodegenerative disorders - adult onset v2.164 SIGMAR1 Ivone Leong Phenotypes for gene: SIGMAR1 were changed from Amyotrophic lateral sclerosis 16, juvenile, 614373 to ?Amyotrophic lateral sclerosis 16, juvenile, OMIM:614373
Neurodegenerative disorders - adult onset v2.163 PRPH Ivone Leong Phenotypes for gene: PRPH were changed from 170710; Amyotrophic lateral sclerosis, susceptibility to to {Amyotrophic lateral sclerosis, susceptibility to}, OMIM:170710
Neurodegenerative disorders - adult onset v2.162 PRKRA Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
early-onset generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa;Early-Onset Generalized Dystonia-Parkinsonism;Dystonia 16;Dystonia;Dystonia 16, 612067;early-Onset Generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa;Early Onset Complex Disease
Neurodegenerative disorders - adult onset v2.162 PRKRA Ivone Leong Phenotypes for gene: PRKRA were changed from early-onset generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa; Early-Onset Generalized Dystonia-Parkinsonism; Dystonia 16; Dystonia; Dystonia 16, 612067; early-Onset Generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa; Early Onset Complex Disease to Dystonia 16, OMIM:612067
Neurodegenerative disorders - adult onset v2.161 NEK1 Ivone Leong Phenotypes for gene: NEK1 were changed from Amyotrophic lateral sclerosis, susceptibility to, 24; 617892 to {Amyotrophic lateral sclerosis, susceptibility to, 24}, OMIM:617892
Neurodegenerative disorders - adult onset v2.160 MATR3 Ivone Leong Phenotypes for gene: MATR3 were changed from Amyotrophic lateral sclerosis 21 to Amyotrophic lateral sclerosis 21, OMIM:606070
Adult onset movement disorder v1.61 PARK7 Arina Puzriakova Phenotypes for gene: PARK7 were changed from 606324; Parkinson disease 7 autosomal recessive early-onset to Parkinson disease 7, autosomal recessive early-onset, OMIM:606324
Neurodegenerative disorders - adult onset v2.159 MARS2 Ivone Leong Phenotypes for gene: MARS2 were changed from Spastic ataxia 3, autosomal recessive to Spastic ataxia 3, autosomal recessive, OMIM:611390
Adult onset movement disorder v1.60 PANK2 Arina Puzriakova Phenotypes for gene: PANK2 were changed from pantothenate kinase-associated neurodegeneration; Neurodegeneration with brain iron accumulation 1; Early Onset Complex Disease; Dystonia; 234200 to Neurodegeneration with brain iron accumulation 1, OMIM:234200
Neurodegenerative disorders - adult onset v2.158 HNRNPA2B1 Ivone Leong Phenotypes for gene: HNRNPA2B1 were changed from Amyotrophic lateral sclerosis to Amyotrophic lateral sclerosis, MONDO:0004976; ?Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, OMIM:615422
Neurodegenerative disorders - adult onset v2.157 GIGYF2 Ivone Leong Phenotypes for gene: GIGYF2 were changed from {Parkinson disease 11}; Susceptibility to Parkinson disease 11, 607688 to {Parkinson disease 11}, OMIM:607688
Neurodegenerative disorders - adult onset v2.156 GCDH Ivone Leong Phenotypes for gene: GCDH were changed from Dystonia; Glutaricaciduria, type I, 231670 to Dystonia; Glutaricaciduria, type I, OMIM:231670
Adult onset movement disorder v1.59 NKX2-1 Arina Puzriakova Phenotypes for gene: NKX2-1 were changed from Choreoathetosis, hypothyroidism, and neonatal respiratory distress; Chorea, hereditary benign 118700 to Choreoathetosis, hypothyroidism, and neonatal respiratory distress, OMIM:610978; Chorea, hereditary benign, OMIM:118700
Neurodegenerative disorders - adult onset v2.155 GBA Ivone Leong Phenotypes for gene: GBA were changed from {Parkinson disease, late-onset, susceptibility to}, 168600; Gaucher disease, type I, 230800 to {Parkinson disease, late-onset, susceptibility to}, OMIM:168600; Gaucher disease, type I, OMIM:230800
Neurodegenerative disorders - adult onset v2.154 EWSR1 Ivone Leong Phenotypes for gene: EWSR1 were changed from Amyotrophic lateral sclerosis to Amyotrophic lateral sclerosis, MONDO:0004976
Neurodegenerative disorders - adult onset v2.153 EIF4G1 Ivone Leong Phenotypes for gene: EIF4G1 were changed from Parkinsons disease 18, 614251 to {Parkinsons disease 18}, OMIM:614251
Neurodegenerative disorders - adult onset v2.152 DAO Ivone Leong Phenotypes for gene: DAO were changed from Amyotrophic lateral sclerosis to Amyotrophic lateral sclerosis, MONDO:0004976
Neurodegenerative disorders - adult onset v2.151 COQ2 Ivone Leong Phenotypes for gene: COQ2 were changed from Multiple system atrophy, susceptibility to, 146500 to {Multiple system atrophy, susceptibility to}, OMIM:146500
Neurodegenerative disorders - adult onset v2.150 CIZ1 Ivone Leong Phenotypes for gene: CIZ1 were changed from Dystonia 23, 614860 to Dystonia 23, MONDO:0013928
Neurodegenerative disorders - adult onset v2.149 CIZ1 Ivone Leong Publications for gene: CIZ1 were set to
Neurodegenerative disorders - adult onset v2.148 CCDC88C Ivone Leong Phenotypes for gene: CCDC88C were changed from autosomal dominant spinocerebellar ataxia to ?Spinocerebellar ataxia 40, OMIM:616053
Neurodegenerative disorders - adult onset v2.147 ATP6AP2 Ivone Leong Phenotypes for gene: ATP6AP2 were changed from ?Parkinsonism with spasticity, X-linked 300911; Mental retardation, X-linked, syndromic, Hedera type 300423 to ?Parkinsonism with spasticity, X-linked, OMIM:300911; Mental retardation, X-linked, syndromic, Hedera type, OMIM:300423
Neurodegenerative disorders - adult onset v2.146 ATP2B3 Ivone Leong Phenotypes for gene: ATP2B3 were changed from Spinocerebellar ataxia, X-linked 1 to ?Spinocerebellar ataxia, X-linked 1, OMIM:302500
Neurodegenerative disorders - adult onset v2.145 ARHGEF28 Ivone Leong Phenotypes for gene: ARHGEF28 were changed from Amyotrophic lateral sclerosis to Amyotrophic lateral sclerosis, MONDO:0004976
Neurodegenerative disorders - adult onset v2.144 AP5Z1 Ivone Leong Phenotypes for gene: AP5Z1 were changed from Spastic Paraplegia, Recessive; Spastic paraplegia 48, autosomal recessive to Spastic paraplegia 48, autosomal recessive, OMIM:613647
Neurodegenerative disorders - adult onset v2.143 XPR1 Ivone Leong Phenotypes for gene: XPR1 were changed from to Basal ganglia calcification, idiopathic, 6, OMIM:605237
Neurodegenerative disorders - adult onset v2.142 WDR45 Ivone Leong Phenotypes for gene: WDR45 were changed from Dystonia; beta-propeller protein-associated neurodegeneration to Dystonia; Neurodegeneration with brain iron accumulation 5, OMIM:300894
Neurodegenerative disorders - adult onset v2.141 VPS35 Ivone Leong Phenotypes for gene: VPS35 were changed from Parkinson disease 17, 614203; Parkinson Disease, Dominant; late onset parkinson disease; PARKINSON DISEASE 17; PARK17 to {Parkinson disease 17}, OMIM:614203
Neurodegenerative disorders - adult onset v2.140 VPS13A Ivone Leong Phenotypes for gene: VPS13A were changed from Choreoacanthocytosis, OMIM:200150 to Choreoacanthocytosis, OMIM:200150
Neurodegenerative disorders - adult onset v2.139 VPS13A Ivone Leong Phenotypes for gene: VPS13A were changed from complex parkinsonism; Complex parkinsonism; 200150; Choreoacanthocytosis to Choreoacanthocytosis, OMIM:200150
Neurodegenerative disorders - adult onset v2.138 VCP Ivone Leong Phenotypes for gene: VCP were changed from Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia, 613954; familial amyotrophic lateral sclerosis (ALS14); Amyotrophic Lateral Sclerosis, Dominant to Frontotemporal dementia and/or amyotrophic lateral sclerosis 6, OMIM:613954
Neurodegenerative disorders - adult onset v2.137 VAPB Ivone Leong Phenotypes for gene: VAPB were changed from Amyotrophic lateral sclerosis 8, 608627; Amyotrophic Lateral Sclerosis, Dominant to Amyotrophic lateral sclerosis 8, OMIM:608627
Neurodegenerative disorders - adult onset v2.136 UBQLN2 Ivone Leong Phenotypes for gene: UBQLN2 were changed from Amyotrophic Lateral Sclerosis, Dominant; Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia, 300857 to Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia, OMIM:300857
Neurodegenerative disorders - adult onset v2.135 TYROBP Ivone Leong Phenotypes for gene: TYROBP were changed from Dementia to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, OMIM:221770
Neurodegenerative disorders - adult onset v2.134 TTC19 Ivone Leong Phenotypes for gene: TTC19 were changed from Mitochondrial complex III deficiency, nuclear type 2, 615157 to Mitochondrial complex III deficiency, nuclear type 2, OMIM:615157
Neurodegenerative disorders - adult onset v2.133 TREM2 Ivone Leong Phenotypes for gene: TREM2 were changed from Dementia; Dystonia to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, OMIM:618193; Dystonia
Neurodegenerative disorders - adult onset v2.132 TMEM240 Ivone Leong Phenotypes for gene: TMEM240 were changed from Spinocerebellar ataxia 21, 607454 to Spinocerebellar ataxia 21, OMIM:607454
Neurodegenerative disorders - adult onset v2.131 TBK1 Ivone Leong Phenotypes for gene: TBK1 were changed from FTLD; ALS; fronto-temporal dementia; Amyotrophic lateral sclerosis to Frontotemporal dementia and/or amyotrophic lateral sclerosis 4, OMIM:616439
Neurodegenerative disorders - adult onset v2.130 TARDBP Ivone Leong Phenotypes for gene: TARDBP were changed from Amyotrophic Lateral Sclerosis, Dominant; Frontotemporal Dementia; Amyotrophic lateral sclerosis 10, with or without FTD, 612069 to Amyotrophic lateral sclerosis 10, with or without FTD, OMIM:612069
Neurodegenerative disorders - adult onset v2.129 SYNJ1 Ivone Leong Phenotypes for gene: SYNJ1 were changed from Parkinson disease 20, early-onset, 615530; Early Onset Complex Disease; juvenile Parkinsonism; Parkinson disease 20, early-onset to Parkinson disease 20, early-onset, OMIM:615530
Neurodegenerative disorders - adult onset v2.128 SQSTM1 Ivone Leong Phenotypes for gene: SQSTM1 were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 3, OMIM:616437
Neurodegenerative disorders - adult onset v2.127 SPG11 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
early onset parkinsonism, levo dopa responsve;Spastic paraplegia 11, autosomal recessive;Complex parkinsonism;hereditary spastic paraparesis;Early Onset Complex Disease
Neurodegenerative disorders - adult onset v2.127 SPG11 Ivone Leong Phenotypes for gene: SPG11 were changed from early onset parkinsonism, levo dopa responsve; Spastic paraplegia 11, autosomal recessive; Complex parkinsonism; hereditary spastic paraparesis; Early Onset Complex Disease to early onset parkinsonism, levo dopa responsve; Spastic paraplegia 11, autosomal recessive, OMIM:604360; Complex parkinsonism; hereditary spastic paraparesis; Amyotrophic lateral sclerosis 5, juvenile, OMIM:602099
Neurodegenerative disorders - adult onset v2.126 SPAST Ivone Leong Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant to Spastic paraplegia 4, autosomal dominant, OMIM:182601
Neurodegenerative disorders - adult onset v2.125 SOD1 Ivone Leong Phenotypes for gene: SOD1 were changed from Amyotrophic lateral sclerosis 1, 105400; amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis, Dominant to Amyotrophic lateral sclerosis 1, OMIM:105400
Neurodegenerative disorders - adult onset v2.124 SNCA Ivone Leong Phenotypes for gene: SNCA were changed from Autosomal dominant Parkinson's disease with alpha-synuclein rearrangements (PARK1/4); Parkinson disease 4, 605543; Parkinson disease 1, 168601; Dementia, Lewy body, 127750 to Parkinson disease 4, OMIM:605543; Parkinson disease 1, OMIM:168601; Dementia, Lewy body, OMIM:127750
Neurodegenerative disorders - adult onset v2.123 SLC20A2 Ivone Leong Phenotypes for gene: SLC20A2 were changed from Dystonia; Basal ganglia calcification, idiopathic, 1, 158378 to Dystonia; Basal ganglia calcification, idiopathic, 1, OMIM:158378
Neurodegenerative disorders - adult onset v2.122 SETX Ivone Leong Phenotypes for gene: SETX were changed from Amyotrophic lateral sclerosis 4, juvenile 602433; ataxia with oculomotor apraxia type 2 (AOA2), juvenile amyotrophic lateral sclerosis (ALS4) and autosomal dominant ataxia; Ataxia-ocular apraxia-2 to Amyotrophic lateral sclerosis 4, juvenile, OMIM:602433
Neurodegenerative disorders - adult onset v2.121 RNF216 Ivone Leong Phenotypes for gene: RNF216 were changed from Cerebellar ataxia and hypogonadotropic hypogonadism, 212840 to Cerebellar ataxia and hypogonadotropic hypogonadism, OMIM:212840
Neurodegenerative disorders - adult onset v2.120 PSEN2 Ivone Leong Phenotypes for gene: PSEN2 were changed from Dementia to Alzheimer disease-4, OMIM:606889
Neurodegenerative disorders - adult onset v2.119 PSEN1 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Acne inversa, familial, 3, 613737;Alzheimer disease, type 3, with spastic paraparesis and unusual plaques, 607822;Alzheimer disease, type 3, with spastic paraparesis and apraxia, 607822;Alzheimer disease, type 3, with spastic paraparesis and unusual plaques;Dystonia;Dementia, frontotemporal, 600274;Pick disease, 172700;Clinical syndrome Alzheimer disease;Alzheimer disease, type 3, 607822;Cardiomyopathy, dilated, 1U, 613694;Alzheimer disease, type 3, with spastic paraparesis and apraxia
Neurodegenerative disorders - adult onset v2.119 PSEN1 Ivone Leong Phenotypes for gene: PSEN1 were changed from Acne inversa, familial, 3, 613737; Alzheimer disease, type 3, with spastic paraparesis and unusual plaques, 607822; Alzheimer disease, type 3, with spastic paraparesis and apraxia, 607822; Alzheimer disease, type 3, with spastic paraparesis and unusual plaques; Dystonia; Dementia, frontotemporal, 600274; Pick disease, 172700; Clinical syndrome Alzheimer disease; Alzheimer disease, type 3, 607822; Cardiomyopathy, dilated, 1U, 613694; Alzheimer disease, type 3, with spastic paraparesis and apraxia to Alzheimer disease, type 3, with spastic paraparesis and unusual plaques, OMIM:607822; Alzheimer disease, type 3, with spastic paraparesis and apraxia, OMIM:607822; Dystonia; Dementia, frontotemporal, OMIM:600274; Pick disease, OMIM:172700; Alzheimer disease, type 3, OMIM:607822
Neurodegenerative disorders - adult onset v2.118 PRNP Ivone Leong Phenotypes for gene: PRNP were changed from Creutzfeldt-Jakob disease; Autosomal Dominant Ataxia; Insomnia, fatal familial; Huntington disease-like 1; Clinical syndrome Prion disease; Dementia; Gerstmann-Straussler disease to Creutzfeldt-Jakob disease, OMIM:123400; Huntington disease-like 1, OMIM:603218; Dementia; Gerstmann-Straussler disease, OMIM:137440
Neurodegenerative disorders - adult onset v2.117 PRKN Ivone Leong Phenotypes for gene: PRKN were changed from Parkinson disease, juvenile, type 2; Dystonia; Parkinson Disease 2, Autosomal Recessive Juvenile; juvenile parkinsonism/dystonia; Parkinson Disease, Juvenile to Parkinson disease, juvenile, type 2, OMIM:600116; Dystonia
Neurodegenerative disorders - adult onset v2.116 PLA2G6 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Infantile neuroaxonal dystrophy 1, 256600;PLA2G6-associated neurodegeneration;Neurodegeneration with brain iron accumulation 2B, 610217;Infantile neuroaxonal dystrophy 1 (#256600);Neurodegeneration with brain iron accumulation 2B (#610217);Parkinson disease 14 (#612953);Parkinson disease 14, 612953;Early Onset Complex Disease
Neurodegenerative disorders - adult onset v2.116 PLA2G6 Ivone Leong Phenotypes for gene: PLA2G6 were changed from Infantile neuroaxonal dystrophy 1, 256600; PLA2G6-associated neurodegeneration; Neurodegeneration with brain iron accumulation 2B, 610217; Infantile neuroaxonal dystrophy 1 (#256600); Neurodegeneration with brain iron accumulation 2B (#610217); Parkinson disease 14 (#612953); Parkinson disease 14, 612953; Early Onset Complex Disease to Infantile neuroaxonal dystrophy 1, OMIM:256600; Neurodegeneration with brain iron accumulation 2B, OMIM:610217; Parkinson disease 14, OMIM:612953
Neurodegenerative disorders - adult onset v2.115 PINK1 Ivone Leong Phenotypes for gene: PINK1 were changed from Parkinson disease 6, early onset, 605909; Dystonia; Parkinson Disease 6, Autosomal Recessive Early-Onset to Parkinson disease 6, early onset, OMIM:605909; Dystonia
Neurodegenerative disorders - adult onset v2.114 PFN1 Ivone Leong Phenotypes for gene: PFN1 were changed from Amyotrophic lateral sclerosis 18, 614808 to Amyotrophic lateral sclerosis 18, OMIM:614808
Adult onset movement disorder v1.58 MAPT Arina Puzriakova Phenotypes for gene: MAPT were changed from Supranuclear palsy, progressive, 601104; clinical presentation suggestive of cortico-basal/PSP syndrome; Supranuclear palsy, progressive atypical, 260540; {Parkinson disease, susceptibility to}, 168600; Pick disease, 172700; Tauopathy and r; Dementia, frontotemporal, with or without parkinsonism, 600274; PARKINSON-DEMENTIA SYNDROME to Supranuclear palsy, progressive, OMIM:601104; Supranuclear palsy, progressive atypical, OMIM:260540; {Parkinson disease, susceptibility to}, OMIM:168600; Dementia, frontotemporal, with or without parkinsonism, OMIM:600274; Pick disease, OMIM:172700
Neurodegenerative disorders - adult onset v2.113 PDGFRB Ivone Leong Phenotypes for gene: PDGFRB were changed from Dystonia; Basal ganglia calcification, idiopathic, 4, 615007 to Dystonia; Basal ganglia calcification, idiopathic, 4, OMIM:615007
Neurodegenerative disorders - adult onset v2.112 PDGFB Ivone Leong Phenotypes for gene: PDGFB were changed from to Basal ganglia calcification, idiopathic, 5, OMIM:615483
Neurodegenerative disorders - adult onset v2.111 PARK7 Ivone Leong Phenotypes for gene: PARK7 were changed from Parkinson disease 7 autosomal recessive early-onset; 606324; Parkinson disease 7, autosomal recessive early-onset to Parkinson disease 7, autosomal recessive early-onset, OMIM:606324
Neurodegenerative disorders - adult onset v2.110 PANK2 Ivone Leong Phenotypes for gene: PANK2 were changed from Dystonia; Neurodegeneration with brain iron accumulation 1; 234200; Early Onset Complex Disease; pantothenate kinase-associated neurodegeneration to Dystonia; Neurodegeneration with brain iron accumulation 1, OMIM:234200
Neurodegenerative disorders - adult onset v2.109 OPTN Ivone Leong Phenotypes for gene: OPTN were changed from Glaucoma 1, open angle, E, 137760; Amyotrophic Lateral Sclerosis, Recessive to Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia, OMIM:613435
Neurodegenerative disorders - adult onset v2.108 NPC2 Ivone Leong Phenotypes for gene: NPC2 were changed from Dystonia; Niemann-Pick disease type C2 (#607625) to Dystonia; Niemann-Pick disease, type C2, OMIM:607625
Neurodegenerative disorders - adult onset v2.107 NPC1 Ivone Leong Phenotypes for gene: NPC1 were changed from Niemann-Pick disease types C1 and D (#257220) to Niemann-Pick disease, type C1, OMIM:257220; Niemann-Pick disease, type D, OMIM:257220
Adult onset movement disorder v1.57 LYST Arina Puzriakova Phenotypes for gene: LYST were changed from albinism; peripheral neuropathy; Chediak-Higashi syndrome 214500; Parkinsonism to Chediak-Higashi syndrome, OMIM:214500
Neurodegenerative disorders - adult onset v2.106 NOTCH3 Ivone Leong Phenotypes for gene: NOTCH3 were changed from Dementia to Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, OMIM:125310
Neurodegenerative disorders - adult onset v2.105 NHLRC1 Ivone Leong Phenotypes for gene: NHLRC1 were changed from Epilepsy, progressive myoclonic 2B (Lafora) 254780 to Epilepsy, progressive myoclonic 2B (Lafora), OMIM:254780
Neurodegenerative disorders - adult onset v2.104 MAPT Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Dementia, frontotemporal, with or without parkinsonism, 600274;Supranuclear palsy, progressive, OMIM:601104;clinical presentation suggestive of cortico-basal/PSP syndrome;Parkinson disease, susceptibility to}, OMIM:168600;Pick disease, OMIM:172700;Clinical syndrome FTLD (Frontotemporal lobar degeneration);Supranuclear palsy, progressive atypical, OMIM:260540
Neurodegenerative disorders - adult onset v2.104 MAPT Ivone Leong Phenotypes for gene: MAPT were changed from Dementia, frontotemporal, with or without parkinsonism, 600274; Tauopathy and r; Supranuclear palsy, progressive, 601104; clinical presentation suggestive of cortico-basal/PSP syndrome; PARKINSON-DEMENTIA SYNDROME; {Parkinson disease, susceptibility to}, 168600; Pick disease, 172700; Clinical syndrome FTLD (Frontotemporal lobar degeneration); Supranuclear palsy, progressive atypical, 260540 to Dementia, frontotemporal, with or without parkinsonism, OMIM:600274; Tauopathy and r; Supranuclear palsy, progressive, 601104; clinical presentation suggestive of cortico-basal/PSP syndrome; PARKINSON-DEMENTIA SYNDROME; {Parkinson disease, susceptibility to}, 168600; Pick disease, 172700; Clinical syndrome FTLD (Frontotemporal lobar degeneration); Supranuclear palsy, progressive atypical, 260540
Adult onset movement disorder v1.56 LRRK2 Arina Puzriakova Phenotypes for gene: LRRK2 were changed from LRRK2 G2019S mutation; Parkinson Disease, Dominant; Parkinson disease 8, 607060; PARKINSON DISEASE 8, AUTOSOMAL DOMINANT; Autosomal dominant Parkinson's disease; Parkinson Disease 8, Autosomal Dominant to {Parkinson disease 8}, OMIM:607060
Adult onset movement disorder v1.55 KMT2B Arina Puzriakova Phenotypes for gene: KMT2B were changed from Dystonia 28, childhood-onset 617284; early-onset dystonia to Dystonia 28, childhood-onset, OMIM:617284
Neurodegenerative disorders - adult onset v2.103 LYST Ivone Leong Phenotypes for gene: LYST were changed from Chediak-Higashi syndrome, OMIM:214500; peripheral neuropathy; Parkinsonism; albinism; spastic paraplegia to Chediak-Higashi syndrome, OMIM:214500; peripheral neuropathy; Parkinsonism; spastic paraplegia
Neurodegenerative disorders - adult onset v2.102 LYST Ivone Leong Phenotypes for gene: LYST were changed from Chediak-Higashi syndrome 214500; peripheral neuropathy; Parkinsonism; albinism; spastic paraplegia to Chediak-Higashi syndrome, OMIM:214500; peripheral neuropathy; Parkinsonism; albinism; spastic paraplegia
Neurodegenerative disorders - adult onset v2.101 LRRK2 Ivone Leong Phenotypes for gene: LRRK2 were changed from Parkinson Disease 8, Autosomal Dominant; Autosomal dominant Parkinson's disease; Parkinson Disease, Dominant; PARKINSON DISEASE 8, AUTOSOMAL DOMINANT; LRRK2 G2019S mutation; Parkinson disease 8, 607060 to LRRK2 G2019S mutation; {Parkinson disease 8}, OMIM:607060
Neurodegenerative disorders - adult onset v2.100 KIF5A Ivone Leong Phenotypes for gene: KIF5A were changed from Spastic paraplegia 10, autosomal dominant to Spastic paraplegia 10, autosomal dominant, OMIM:604187
Neurodegenerative disorders - adult onset v2.99 KIAA1161 Ivone Leong Phenotypes for gene: KIAA1161 were changed from Autosomal Recessive Primary Familial Brain Calcification; Basal ganglia calcification, idiopathic, 7, autosomal recessive, 618317 to Basal ganglia calcification, idiopathic, 7, autosomal recessive, OMIM:618317
Adult onset movement disorder v1.54 KIAA1161 Arina Puzriakova Phenotypes for gene: KIAA1161 were changed from Autosomal Recessive Primary Familial Brain Calcification; Basal ganglia calcification, idiopathic, 7, autosomal recessive; Abnormal movements; Dystonia to Basal ganglia calcification, idiopathic, 7, autosomal recessive, OMIM:618317
Adult onset movement disorder v1.53 HPCA Arina Puzriakova Phenotypes for gene: HPCA were changed from Dystonia 2, torsion, autosomal recessive, 224500; generalized dystonia with additional neurological features; childhood-onset generalized dystonia; adolescence-onset segmental dystonia to Dystonia 2, torsion, autosomal recessive, OMIM:224500
Adult onset movement disorder v1.52 GTPBP2 Arina Puzriakova Phenotypes for gene: GTPBP2 were changed from Jaberi-Elahi syndrome, 617988; Dystonia to Jaberi-Elahi syndrome, OMIM:617988
Neurodegenerative disorders - adult onset v2.98 KCND3 Ivone Leong Phenotypes for gene: KCND3 were changed from Spinocerebellarataxia19,607346 to Spinocerebellarataxia19, OMIM:607346
Neurodegenerative disorders - adult onset v2.97 KCNC3 Ivone Leong Phenotypes for gene: KCNC3 were changed from Spinocerebellar ataxia 13 to Spinocerebellar ataxia 13, OMIM:605259
Neurodegenerative disorders - adult onset v2.96 ITM2B Ivone Leong Phenotypes for gene: ITM2B were changed from Dementia, familial British, 176500 to Dementia, familial British, OMIM:176500
Neurodegenerative disorders - adult onset v2.95 ITM2B Ivone Leong Publications for gene: ITM2B were set to 29525180; 10391242
Neurodegenerative disorders - adult onset v2.94 HTRA1 Ivone Leong Phenotypes for gene: HTRA1 were changed from Dementia; CARASIL syndrome 600142; Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2 616779 to dementia (disease), MONDO:0001627; CARASIL syndrome, OMIM:600142; Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2, OMIM:616779
Adult onset movement disorder v1.51 GRN Arina Puzriakova Phenotypes for gene: GRN were changed from Complex parkinsonism; frontotemporal lobar degeneration with TDP43 inclusions; clinical presentation suggestive of cortico-basal/PSP syndrome to Frontotemporal lobar degeneration with ubiquitin-positive inclusions, OMIM:607485
Neurodegenerative disorders - adult onset v2.93 HNRNPA1 Ivone Leong Phenotypes for gene: HNRNPA1 were changed from ?Inclusion body myopathy wtih early-onset Paget disease without frontotemporal to ?Inclusion body myopathy wtih early-onset Paget disease without frontotemporal dementia type 3, OMIM:615424, Amyotrophic lateral sclerosis 20, OMIM:615426
Neurodegenerative disorders - adult onset v2.92 HNRNPA1 Ivone Leong Publications for gene: HNRNPA1 were set to 23455423
Adult onset movement disorder v1.50 GNAL Arina Puzriakova Phenotypes for gene: GNAL were changed from adult-onset cranio-cervical dystonia; Dystonia 25, 615073 to Dystonia 25, OMIM:615073
Adult onset movement disorder v1.49 GFAP Arina Puzriakova Phenotypes for gene: GFAP were changed from Alexander disease 203450 to Alexander disease, OMIM:203450
Adult onset movement disorder v1.48 GCH1 Arina Puzriakova Phenotypes for gene: GCH1 were changed from Hyperphenylalaninemia, BH4-deficient, B, 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230; Dopa-Responsive Dystonia (DRD) to Hyperphenylalaninemia, BH4-deficient, B, OMIM:233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, OMIM:128230
Neurodegenerative disorders - adult onset v2.91 HEXA Ivone Leong Phenotypes for gene: HEXA were changed from GM2-gangliosidosis, several forms, 272800; Tay-Sachs disease, 272800 to GM2-gangliosidosis, several forms, OMIM:272800; Tay-Sachs disease, OMIM:272800
Neurodegenerative disorders - adult onset v2.90 GRN Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
clinical presentation suggestive of cortico-basal/PSP syndrome;Complex parkinsonism;Frontotemporal Dementia;frontotemporal lobar degeneration with TDP43 inclusions;Clinical syndrome FTLD (Frontotemporal lobar degeneration)
Neurodegenerative disorders - adult onset v2.90 GRN Ivone Leong Phenotypes for gene: GRN were changed from clinical presentation suggestive of cortico-basal/PSP syndrome; Complex parkinsonism; Frontotemporal Dementia; frontotemporal lobar degeneration with TDP43 inclusions; Clinical syndrome FTLD (Frontotemporal lobar degeneration) to Frontotemporal lobar degeneration with ubiquitin-positive inclusions, OMIM:607485; Aphasia, primary progressive, OMIM:607485
Neurodegenerative disorders - adult onset v2.89 GFAP Ivone Leong Phenotypes for gene: GFAP were changed from Autosomal Dominant Ataxia; Alexander disease to Autosomal Dominant Ataxia; Alexander disease, OMIM:203450
Neurodegenerative disorders - adult onset v2.88 GCH1 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Dopa-Responsive Dystonia (DRD);progressive spastic paraplegia;Dystonia;Hyperphenylalaninemia, BH4-deficient, B, 233910;Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230;Spastic paraplegia
Neurodegenerative disorders - adult onset v2.88 GCH1 Ivone Leong Phenotypes for gene: GCH1 were changed from Dopa-Responsive Dystonia (DRD); progressive spastic paraplegia; Dystonia; Hyperphenylalaninemia, BH4-deficient, B, 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230; Spastic paraplegia to Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, OMIM:128230; Hyperphenylalaninemia, BH4-deficient, B, OMIM:233910; Spastic paraplegia
Adult onset movement disorder v1.47 GBA Arina Puzriakova Phenotypes for gene: GBA were changed from {Parkinson disease, late-onset, susceptibility to}, 168600 to {Parkinson disease, late-onset, susceptibility to}, OMIM:168600
Neurodegenerative disorders - adult onset v2.87 GCH1 Ivone Leong Publications for gene: GCH1 were set to 25497597; http://www.ncbi.nlm.nih.gov/books/NBK1155/; 24509643; 24993959; 21935284
Adult onset movement disorder v1.46 FTL Arina Puzriakova Phenotypes for gene: FTL were changed from Neurodegeneration with brain iron accumulation 3 606159; movement disorder to Neurodegeneration with brain iron accumulation 3, OMIM:606159
Adult onset movement disorder v1.45 FTL Arina Puzriakova Publications for gene: FTL were set to http://www.ncbi.nlm.nih.gov/pubmed/24209436; 24209436
Neurodegenerative disorders - adult onset v2.86 FUS Ivone Leong Phenotypes for gene: FUS were changed from Dementia; Amyotrophic lateral sclerosis 6, autosomal recessive, with or without frontotemporal; Amyotrophic Lateral Sclerosis, Dominant to Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia, OMIM:608030
Neurodegenerative disorders - adult onset v2.85 FTL Ivone Leong Phenotypes for gene: FTL were changed from Neurodegeneration with brain iron accumulation 3; movement disorder to Neurodegeneration with brain iron accumulation 3, OMIM:606159
Neurodegenerative disorders - adult onset v2.84 FTL Ivone Leong Publications for gene: FTL were set to 24209436; http://www.ncbi.nlm.nih.gov/pubmed/24209436
Neurodegenerative disorders - adult onset v2.83 FIG4 Ivone Leong Phenotypes for gene: FIG4 were changed from Charcot-Marie-Tooth disease, type 4J, 611228; Amyotrophic Lateral Sclerosis, Dominant to Charcot-Marie-Tooth disease, type 4J, OMIM:611228; Amyotrophic lateral sclerosis 11, OMIM:612577
Neurodegenerative disorders - adult onset v2.82 FBXO7 Ivone Leong Phenotypes for gene: FBXO7 were changed from Parkinson Disease, Recessive; Dystonia; juvenile parkinsonism; parkinsonian-pyramidal syndrome; Parkinson disease 15, autosomal recessive, 260300; Early Onset Complex Disease to Dystonia; Parkinson disease 15, autosomal recessive, OMIM:260300
Neurodegenerative disorders - adult onset v2.81 EPM2A Ivone Leong Phenotypes for gene: EPM2A were changed from Epilepsy, progressive myoclonic 2A (Lafora) 254780 to Epilepsy, progressive myoclonic 2A (Lafora), OMIM:254780
Neurodegenerative disorders - adult onset v2.80 ELOVL4 Ivone Leong Phenotypes for gene: ELOVL4 were changed from Spinocerebellar ataxia 34 133190 to Spinocerebellar ataxia 34, OMIM:133190
Neurodegenerative disorders - adult onset v2.79 EIF2B5 Ivone Leong Phenotypes for gene: EIF2B5 were changed from Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease to Leukoencephalopathy with vanishing white matter, OMIM:603896
Neurodegenerative disorders - adult onset v2.78 EIF2B4 Ivone Leong Phenotypes for gene: EIF2B4 were changed from Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease to Leukoencephalopathy with vanishing white matter, OMIM:603896
Neurodegenerative disorders - adult onset v2.77 EIF2B3 Ivone Leong Phenotypes for gene: EIF2B3 were changed from Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease to Leukoencephalopathy with vanishing white matter, OMIM:603896
Adult onset movement disorder v1.44 FBXO7 Arina Puzriakova Phenotypes for gene: FBXO7 were changed from Parkinson disease 15, autosomal recessive, 260300; Parkinson Disease, Recessive; Early Onset Complex Disease; juvenile parkinsonism; Dystonia; parkinsonian-pyramidal syndrome to Parkinson disease 15, autosomal recessive, OMIM:260300
Neurodegenerative disorders - adult onset v2.76 EIF2B2 Ivone Leong Phenotypes for gene: EIF2B2 were changed from Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease; Leukoencephalopathy with vanishing white matter, 603896 to Leukoencephalopathy with vanishing white matter, OMIM:603896
Neurodegenerative disorders - adult onset v2.75 EIF2B1 Ivone Leong Phenotypes for gene: EIF2B1 were changed from Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease; Childhood Ataxia with Central Nervous System Hypomyelination/Vanishing White Matter to Leukoencephalopathy with vanishing white matter, OMIM:603896
Neurodegenerative disorders - adult onset v2.74 DNMT1 Ivone Leong Phenotypes for gene: DNMT1 were changed from Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, OMIM; 604121 to Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, OMIM:604121
Neurodegenerative disorders - adult onset v2.73 DNMT1 Ivone Leong Phenotypes for gene: DNMT1 were changed from Dementia, Deafness, and Sensory Neuropathy; Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, to Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant, OMIM; 604121
Adult onset movement disorder v1.43 DNAJC6 Arina Puzriakova Phenotypes for gene: DNAJC6 were changed from Parkinson disease 19a, juvenile-onset; Parkinson disease 19, juvenile-onset, 615528; Parkinson disease 19b, early-onset to Parkinson disease 19, juvenile-onset, OMIM:615528; Parkinson disease 19b, early-onset, OMIM:615528
Neurodegenerative disorders - adult onset v2.72 DNAJC6 Ivone Leong Phenotypes for gene: DNAJC6 were changed from Parkinson disease 19b, early-onset; Parkinson disease 19, juvenile-onset, 615528; Parkinson disease 19a, juvenile-onset to Parkinson disease 19b, early-onset, OMIM:615528; Parkinson disease 19a, juvenile-onset, OMIM:615528
Neurodegenerative disorders - adult onset v2.71 DNAJC5 Ivone Leong Phenotypes for gene: DNAJC5 were changed from Ceroid lipofuscinosis, neuronal, 4, Parry type 162350 to Ceroid lipofuscinosis, neuronal, 4, Parry type, OMIM:162350
Neurodegenerative disorders - adult onset v2.70 DCTN1 Ivone Leong Phenotypes for gene: DCTN1 were changed from Neuropathy, distal hereditary motor, type VIIB, 607641; Perry syndrome; Neuropathy, distal hereditary motor, type VIIB; Perry syndrome, 168605; {Amyotrophic lateral sclerosis, susceptibility to}, 105400 to Neuropathy, distal hereditary motor, type VIIB, OMIM:607641; Perry syndrome, OMIM:168605; {Amyotrophic lateral sclerosis, susceptibility to}, OMIM:105400
Neurodegenerative disorders - adult onset v2.69 DCTN1 Ivone Leong Publications for gene: DCTN1 were set to 26954557; 25109764; 20437543; 24343258; 27132499; 20945553 (Gene Reviews); 27346608; 19136952
Neurodegenerative disorders - adult onset v2.68 DARS2 Ivone Leong Phenotypes for gene: DARS2 were changed from Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, 611105 to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105
Neurodegenerative disorders - adult onset v2.67 CYP7B1 Ivone Leong Phenotypes for gene: CYP7B1 were changed from Spastic paraplegia 5A, autosomal recessive to Spastic paraplegia 5A, autosomal recessive, OMIM:270800
Neurodegenerative disorders - adult onset v2.66 CYP27A1 Ivone Leong Phenotypes for gene: CYP27A1 were changed from Cerebrotendinous xanthomatosis, 213700; progressive lower extremity spasticity,often disproportionate to any degree of weakness to Cerebrotendinous xanthomatosis, OMIM:213700; progressive lower extremity spasticity,often disproportionate to any degree of weakness
Neurodegenerative disorders - adult onset v2.65 CTSF Ivone Leong Phenotypes for gene: CTSF were changed from Ceroid lipofuscinosis, neuronal, 13, Kufs type 615362 to Ceroid lipofuscinosis, neuronal, 13, Kufs type, OMIM:615362
Neurodegenerative disorders - adult onset v2.64 CSF1R Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
dementia, motor dysfunction (can include spasticity, ataxia, and parkinsonism) and epilepsy;Dementia;diffuse leukoencephalopathy with spheroids
Neurodegenerative disorders - adult onset v2.64 CSF1R Ivone Leong Phenotypes for gene: CSF1R were changed from dementia, motor dysfunction (can include spasticity, ataxia, and parkinsonism) and epilepsy; Dementia; diffuse leukoencephalopathy with spheroids to dementia, motor dysfunction (can include spasticity, ataxia, and parkinsonism) and epilepsy; Leukoencephalopathy, diffuse hereditary, with spheroids, OMIM:221820
Neurodegenerative disorders - adult onset v2.63 CP Ivone Leong Phenotypes for gene: CP were changed from Dystonia; Aceruloplasminemia; Cerebellar ataxia, 604290; Hemosiderosis, systemic, due to aceruloplasminemia, 604290 to Dystonia; Cerebellar ataxia, OMIM:604290; Hemosiderosis, systemic, due to aceruloplasminemia, OMIM:604290
Neurodegenerative disorders - adult onset v2.62 COASY Ivone Leong Phenotypes for gene: COASY were changed from COASY protein-associated neurodegeneration; Neurodegeneration with brain iron accumulation 6 to COASY protein-associated neurodegeneration; Neurodegeneration with brain iron accumulation 6, OMIM:615643
Neurodegenerative disorders - adult onset v2.61 CLN6 Ivone Leong Phenotypes for gene: CLN6 were changed from Ceroid lipofuscinosis, neuronal, 6, 601780; Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, 204300 to Ceroid lipofuscinosis, neuronal, 6, OMIM:601780; Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, OMIM:204300
Neurodegenerative disorders - adult onset v2.60 CLCN2 Ivone Leong Phenotypes for gene: CLCN2 were changed from {Epilepsy, juvenile absence, susceptibility to, 2}, 607628; {Epilepsy, idiopathic generalized, susceptibility to, 11}, 607628; {Epilepsy, juvenile myoclonic, susceptibility to, 8}, 607628; Leukoencephalopathy with ataxia, 615651 to {Epilepsy, juvenile absence, susceptibility to, 2}, OMIM:607628; {Epilepsy, idiopathic generalized, susceptibility to, 11}, OMIM:607628; {Epilepsy, juvenile myoclonic, susceptibility to, 8}, OMIM:607628; Leukoencephalopathy with ataxia, OMIM:615651
Neurodegenerative disorders - adult onset v2.59 CHMP2B Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
familial frontotemporal lobar degeneration (ALS17);Dystonia;Frontotemporal Dementia;Frontotemporal dementia and/or amyotrophic lateral sclerosis 1;Dementia, familial, nonspecific, 600795;Dementia, familial, nonspecific, 600795Amyotrophic lateral sclerosis 17, 614696;Amyotrophic lateral sclerosis 17, 614696
Neurodegenerative disorders - adult onset v2.59 CHMP2B Ivone Leong Phenotypes for gene: CHMP2B were changed from familial frontotemporal lobar degeneration (ALS17); Dystonia; Frontotemporal Dementia; Frontotemporal dementia and/or amyotrophic lateral sclerosis 1; Dementia, familial, nonspecific, 600795; Dementia, familial, nonspecific, 600795Amyotrophic lateral sclerosis 17, 614696; Amyotrophic lateral sclerosis 17, 614696 to Frontotemporal dementia and/or amytrophic lateral sclerosis 7, OMIM:600795; Dystonia
Neurodegenerative disorders - adult onset v2.58 CHCHD2 Ivone Leong Phenotypes for gene: CHCHD2 were changed from Parkinson disease 22, autosomal dominant; 616710 to Parkinson disease 22, autosomal dominant, OMIM:616710
Neurodegenerative disorders - adult onset v2.57 CHCHD2 Ivone Leong Publications for gene: CHCHD2 were set to Funayama, M., Ohe, K., Amo, T., Furuya, N., Yamaguchi, J., Saiki, S., Li, Y., Ogaki, K., Ando, M., Yoshino, H., Tomiyama, H., Nishioka, K., and 12 others. CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study. Lancet Neurol. 14: 274-282, 2015; 25662902; 26067114; 26705026; 26067110
Neurodegenerative disorders - adult onset v2.56 CHCHD10 Ivone Leong Phenotypes for gene: CHCHD10 were changed from ?Myopathy, isolated mitochondrial, autosomal dominant, 616209 to ?Myopathy, isolated mitochondrial, autosomal dominant, OMIM:616209
Neurodegenerative disorders - adult onset v2.55 CCNF Ivone Leong Phenotypes for gene: CCNF were changed from Frontotemporal dementia / amyotrophic lateral sclerosis to Frontotemporal dementia and/or amyotrophic lateral sclerosis 5, OMIM:619141
Neurodegenerative disorders - adult onset v2.54 CACNA1G Ivone Leong Phenotypes for gene: CACNA1G were changed from Spinocerebellar ataxia 42, 61679 to Spinocerebellar ataxia 42, OMIM:616795
Adult onset movement disorder v1.42 DCTN1 Arina Puzriakova Phenotypes for gene: DCTN1 were changed from Perry syndrome to Perry syndrome, OMIM:168605; Neuronopathy, distal hereditary motor, type VIIB, OMIM:607641
Neurodegenerative disorders - adult onset v2.53 C19orf12 Ivone Leong Phenotypes for gene: C19orf12 were changed from mitochondrial membrane protein-associated neurodegeneration; Dystonia; neurodegeneration with brain iron accumulation-4; Neurodegeneration with brain iron accumulation 4 to Dystonia; neurodegeneration with brain iron accumulation-4, OMIM:614298
Neurodegenerative disorders - adult onset v2.52 ATP7B Ivone Leong Phenotypes for gene: ATP7B were changed from Wilson disease 277900; Dystonia; Wilson Disease to Wilson disease, OMIM: 277900; Dystonia
Adult onset movement disorder v1.41 DCAF17 Arina Puzriakova Phenotypes for gene: DCAF17 were changed from Woodhouse-Sakati syndrome; Dystonia to Woodhouse-Sakati syndrome, OMIM:241080
Neurodegenerative disorders - adult onset v2.51 ATP1A3 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
ALTERNATING HEMIPLEGIA OF CHILDHOOD 2, 614820;CAPOS syndrome;DYSTONIA 12, 128235;Dystonia-12;alternating hemiplegia of childhood;Dystonia-12, 128235;Rapid-Onset Dystonia-Parkinsonism;rapid-onset dystonia-parkinsonism;Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss (CAPOS, #601338);Alternating hemiplegia of childhood 2 (#614820) and Dystonia 12 (#128235)
Neurodegenerative disorders - adult onset v2.51 ATP1A3 Ivone Leong Phenotypes for gene: ATP1A3 were changed from ALTERNATING HEMIPLEGIA OF CHILDHOOD 2, 614820; CAPOS syndrome; DYSTONIA 12, 128235; Dystonia-12; alternating hemiplegia of childhood; Dystonia-12, 128235; Rapid-Onset Dystonia-Parkinsonism; rapid-onset dystonia-parkinsonism; Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss (CAPOS, #601338); Alternating hemiplegia of childhood 2 (#614820) and Dystonia 12 (#128235) to ALTERNATING HEMIPLEGIA OF CHILDHOOD 2, OMIM:614820; CAPOS syndrome, OMIM:601338; DYSTONIA 12, OMIM:128235; Rapid-Onset Dystonia-Parkinsonism
Neurodegenerative disorders - adult onset v2.50 ATP13A2 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Parkinson disease 9, 606693;Dystonia;Kufor-Rakeb syndrome;Kufor-Rakeb Syndrome;Parkinson disease;Adult-onset lower-limb predominant spastic paraparesis;Spastic paraplegia 78, autosomal recessive, 617225;complicated hereditary spastic paraplegia
Neurodegenerative disorders - adult onset v2.50 ATP13A2 Ivone Leong Phenotypes for gene: ATP13A2 were changed from Parkinson disease 9, 606693; Dystonia; Kufor-Rakeb syndrome; Kufor-Rakeb Syndrome; Parkinson disease; Adult-onset lower-limb predominant spastic paraparesis; Spastic paraplegia 78, autosomal recessive, 617225; complicated hereditary spastic paraplegia to Kufor-Rakeb syndrome, OMIM:606693; Dystonia; Spastic paraplegia 78, autosomal recessive, OMIM:617225
Neurodegenerative disorders - adult onset v2.49 ARSA Ivone Leong Phenotypes for gene: ARSA were changed from Metachromatic leukodystrophy (#250100); Dystonia to Metachromatic leukodystrophy, OMIM:250100; Dystonia
Neurodegenerative disorders - adult onset v2.48 APP Ivone Leong Phenotypes for gene: APP were changed from Alzheimer disease 1, familial OMIM:104300; Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants OMIM:605714 to Alzheimer disease 1, familial, OMIM:104300; Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants, OMIM:605714
Neurodegenerative disorders - adult onset v2.47 ANXA11 Ivone Leong Phenotypes for gene: ANXA11 were changed from Amytrophic lateral sclerosis 23; 617839 to Amytrophic lateral sclerosis 23, OMIM:617839
Neurodegenerative disorders - adult onset v2.46 ANG Ivone Leong Phenotypes for gene: ANG were changed from Amyotrophic lateral sclerosis 9, 611895; Amyotrophic Lateral Sclerosis, Dominant; familial amyotrophic lateral sclerosis (ALS9) to Amyotrophic lateral sclerosis 9, 611895
Neurodegenerative disorders - adult onset v2.45 ALS2 Ivone Leong Phenotypes for gene: ALS2 were changed from Primary lateral sclerosis, juvenile, 606353; Spastic paralysis, infantile onset ascending, 607225; Amyotrophic lateral sclerosis 2, juvenile, 205100; Amyotrophic Lateral Sclerosis, Recessive to Primary lateral sclerosis, juvenile, 606353; Spastic paralysis, infantile onset ascending, 607225; Amyotrophic lateral sclerosis 2, juvenile, 205100
Adult onset movement disorder v1.40 CYP27A1 Arina Puzriakova Phenotypes for gene: CYP27A1 were changed from Cerebrotendinous xanthomatosis, CTX, 213700; Dystonia; Dystonia, including childhood & adult onset to Cerebrotendinous xanthomatosis, OMIM:213700
Adult onset movement disorder v1.39 CSF1R Arina Puzriakova Publications for gene: CSF1R were set to 23787135
Adult onset movement disorder v1.38 CSF1R Arina Puzriakova Phenotypes for gene: CSF1R were changed from dementia, motor dysfunction (can include spasticity, ataxia, and parkinsonism) and epilepsy; diffuse leukoencephalopathy with spheroids to Leukoencephalopathy, diffuse hereditary, with spheroids, OMIM:221820
Neurodegenerative disorders - adult onset v2.44 AFG3L2 Ivone Leong Phenotypes for gene: AFG3L2 were changed from Spinocerebellar ataxia 28; Spinocerebellar Ataxia, Dominant; Ataxia, spastic, 5, autosomal recessive; Dystonia; Spastic ataxia 5, autosomal recessive to Spinocerebellar ataxia 28, OMIM:610246; Ataxia, spastic, 5, autosomal recessive, OMIM:614487; Dystonia
Adult onset movement disorder v1.37 CP Arina Puzriakova Phenotypes for gene: CP were changed from Cerebellar ataxia 604290; Aceruloplasminemia; Hypoceruloplasminemia, hereditary 604290; Dystonia; Hemosiderosis, systemic, due to aceruloplasminemia 604290 to Cerebellar ataxia, OMIM:604290; Hypoceruloplasminemia, hereditary, OMIM:604290; Hemosiderosis, systemic, due to aceruloplasminemia, OMIM:604290
Neurodegenerative disorders - adult onset v2.43 ABCD1 Ivone Leong Phenotypes for gene: ABCD1 were changed from Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation; spastic paraparesis to Hereditary spastic paraplegia, MONDO:0019064; adrenal failure; VLCFA accumulation; spastic paraparesis
Adult onset movement disorder v1.36 CHMP2B Arina Puzriakova Phenotypes for gene: CHMP2B were changed from familial frontotemporal lobar degeneration (ALS17); Dystonia; Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 7, OMIM:600795
Hydrocephalus v2.99 WNT3 Ivone Leong Phenotypes for gene: WNT3 were changed from Tetra-amelia syndrome to ?Tetra-amelia syndrome 1, OMIM:273395
Hydrocephalus v2.98 TBC1D7 Ivone Leong Phenotypes for gene: TBC1D7 were changed from Macrocephaly/megalencephaly syndrome, autosomal recessive to Macrocephaly/megalencephaly syndrome, autosomal recessive, OMIM:248000
Adult onset movement disorder v1.35 CACNA1A Arina Puzriakova Phenotypes for gene: CACNA1A were changed from familial hemiplegic migraine type 1, 141500; episodic ataxia type 2 (EA2),108500 to Episodic ataxia, type 2, OMIM:108500; Spinocerebellar ataxia 6, OMIM:183086; Migraine, familial hemiplegic, 1, OMIM:141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500
Hydrocephalus v2.97 SEC24D Ivone Leong Phenotypes for gene: SEC24D were changed from Cole-Carpenter syndrome 2 to Cole-Carpenter syndrome 2, OMIM:616294
Hydrocephalus v2.96 SEC24D Ivone Leong Publications for gene: SEC24D were set to 25683121
Hydrocephalus v2.95 PTCH2 Ivone Leong Phenotypes for gene: PTCH2 were changed from Basal cell nevus syndrome to Basal cell nevus syndrome, OMIM:109400
Hydrocephalus v2.94 P4HB Ivone Leong Phenotypes for gene: P4HB were changed from Cole-Carpenter syndrome 1 to Cole-Carpenter syndrome 1, OMIM:112240
Hydrocephalus v2.93 P4HB Ivone Leong Publications for gene: P4HB were set to 25683117
Hydrocephalus v2.92 MTM1 Ivone Leong Phenotypes for gene: MTM1 were changed from Myotubular myopathy, X-linked to Myotubular myopathy, X-linked, OMIM:310400
Hydrocephalus v2.91 MPDZ Ivone Leong Phenotypes for gene: MPDZ were changed from Hydrocephalus, nonsyndromic, autosomal recessive 2, OMIM:615219 to Hydrocephalus, congenital, 2, with or without brain or eye anomalies, OMIM:615219
Hydrocephalus v2.90 MPDZ Ivone Leong Phenotypes for gene: MPDZ were changed from Hydrocephalus, nonsyndromic, autosomal recessive 2 615219 to Hydrocephalus, nonsyndromic, autosomal recessive 2, OMIM:615219
Hydrocephalus v2.89 KIF7 Ivone Leong Phenotypes for gene: KIF7 were changed from ?Hydrolethalus syndrome 2 614120 to ?Hydrolethalus syndrome 2, OMIM:614120
Hydrocephalus v2.88 HDAC6 Ivone Leong Phenotypes for gene: HDAC6 were changed from ?Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia to ?Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia, OMIM:300863
Hydrocephalus v2.87 FLNA Ivone Leong Phenotypes for gene: FLNA were changed from Otopalatodigital syndrome, type II to Otopalatodigital syndrome, type II, OMIM:304120
Hydrocephalus v2.86 EBP Ivone Leong Phenotypes for gene: EBP were changed from MEND syndrome to MEND syndrome, OMIM:300960
Hydrocephalus v2.85 CLIC2 Ivone Leong Phenotypes for gene: CLIC2 were changed from ?Mental retardation, X-linked, syndromic 32 to ?Mental retardation, X-linked, syndromic 32, OMIM:300886
Hydrocephalus v2.84 B3GNT2 Ivone Leong Phenotypes for gene: B3GNT2 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 615287 to muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13, MONDO:0014120
Hydrocephalus v2.83 ARX Ivone Leong Phenotypes for gene: ARX were changed from Hydranencephaly with abnormal genitalia to Hydranencephaly with abnormal genitalia, OMIM:300215
Hydrocephalus v2.82 ZIC3 Ivone Leong Phenotypes for gene: ZIC3 were changed from VACTERL association, X-linked to VACTERL association, X-linked, OMIM:314390
Hydrocephalus v2.81 ZIC2 Ivone Leong Phenotypes for gene: ZIC2 were changed from Holoprosencephaly 5 to Holoprosencephaly 5, OMIM:609637
Hydrocephalus v2.80 ZBTB20 Ivone Leong Phenotypes for gene: ZBTB20 were changed from Primrose syndrome to Primrose syndrome, OMIM:259050
Hydrocephalus v2.79 WASHC5 Ivone Leong Phenotypes for gene: WASHC5 were changed from Ritscher-Schinzel syndrome 1 to Ritscher-Schinzel syndrome 1, OMIM:220210
Hydrocephalus v2.78 USP9X Ivone Leong Phenotypes for gene: USP9X were changed from Mental retardation, X-linked 99 300919 XLR; Mental retardation, X-linked 99, syndromic, female-restricted 300968 to Mental retardation, X-linked 99, OMIM:300919; Mental retardation, X-linked 99, syndromic, female-restricted OMIM:300968
Neurological segmental overgrowth v1.15 PIK3CA Arina Puzriakova Phenotypes for gene: PIK3CA were changed from CLAPO syndrome, somatic, OMIM:613089; CLOVE syndrome, somatic, OMIM:612918; Macrodactyly, somatic, OMIM:155500; Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, OMIM:602501 to Cowden syndrome 5, OMIM:615108; CLAPO syndrome, somatic, OMIM:613089; CLOVE syndrome, somatic, OMIM:612918; Macrodactyly, somatic, OMIM:155500; Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, OMIM:602501
Neurological segmental overgrowth v1.14 PTEN Arina Puzriakova Phenotypes for gene: PTEN were changed from hemihypertrophy; Bannayan Riley Ruvalcalba Syndrome; Bannayan-Riley-Ruvalcaba Syndrome; Proteus-like syndrome; macrocephaly; Bannayan-Riley-Ruvalcaba syndrome, 153480; BRRS; Bannayan-Riley-Ruvalcaba syndrome,153480; megalencephaly; PTEN Hamartoma Tumor Syndrome; Macrocephaly and Overgrowth Syndromes; PHTS; Cowden syndrome to Cowden syndrome 1, OMIM:158350; Lhermitte-Duclos syndrome, OMIM:158350; Macrocephaly/autism syndrome, OMIM:605309
Neurological segmental overgrowth v1.13 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from MPPH1; Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, 603387; Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, 603387; Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus syndrome 1; Macrocephaly and Overgrowth Syndromes to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Neurological segmental overgrowth v1.12 PIK3CA Arina Puzriakova Phenotypes for gene: PIK3CA were changed from Megalencephaly-capillary malformation-polymicrogyria syndrome, 602501; CLOVE syndrome; CLOVES; congenital lipomatous overgrowth, vascular malformations, and epidermal nevi, 612918; Congenital Lipomatous Overgrowth Vascular Malformations, Epidermal Nevi and Scoliosis/Skeletal/Spinal anomalies syndrome; CLOVES syndrome; Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic; Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi; Megalencephaly-Capillary Malformation- Polymicrogyria Syndrome; macrocephaly-capillary malformation (MCM) syndrome; Megalencephaly-Capillary malformation syndrome; Macrocephaly and Overgrowth Syndromes; MCAP to CLAPO syndrome, somatic, OMIM:613089; CLOVE syndrome, somatic, OMIM:612918; Macrodactyly, somatic, OMIM:155500; Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, OMIM:602501
Neurological segmental overgrowth v1.11 CCND2 Arina Puzriakova Phenotypes for gene: CCND2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3, 615938; MPPH3; Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus syndrome 3 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3, OMIM:615938
Neurological segmental overgrowth v1.10 AKT3 Arina Puzriakova Phenotypes for gene: AKT3 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, 615937; Macrocephaly and Overgrowth Syndromes; MPPH2; Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus syndrome 2 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, OMIM:615937; Macrocephaly and Overgrowth Syndromes
Neurological segmental overgrowth v1.9 AKT1 Arina Puzriakova Phenotypes for gene: AKT1 were changed from Proteus syndrome, 176920; Proteus syndrome, somatic,176920; Macrocephaly and Overgrowth Syndromes; Segmental Overgrowth Syndrome; Proteus syndrome to Proteus syndrome, somatic, OMIM:176920; Macrocephaly and Overgrowth Syndromes; Segmental Overgrowth Syndrome; Proteus syndrome
Cardiomyopathies - including childhood onset v1.19 MIB1 Zornitza Stark reviewed gene: MIB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23314057; Phenotypes: Left ventricular noncompaction 7, MIM# 615092, cardiomyopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus v2.77 TWIST1 Ivone Leong Phenotypes for gene: TWIST1 were changed from Saethre-Chotzen syndrome 101400 to Saethre-Chotzen syndrome with or without eyelid anomalies, OMIM:101400
Hydrocephalus v2.76 TMEM5 Ivone Leong Phenotypes for gene: TMEM5 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10 615041 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10, OMIM:615041
Hydrocephalus v2.75 TCF12 Ivone Leong Phenotypes for gene: TCF12 were changed from Craniosynostosis 3 615314 to Craniosynostosis 3, OMIM:615314
Hydrocephalus v2.74 SUMF1 Ivone Leong Phenotypes for gene: SUMF1 were changed from Multiple sulfatase deficiency 272200 to Multiple sulfatase deficiency, OMIM:272200
Hydrocephalus v2.73 SUFU Ivone Leong Phenotypes for gene: SUFU were changed from Basal cell nevus syndrome to Basal cell nevus syndrome, OMIM:109400
Hydrocephalus v2.72 STRADA Ivone Leong Phenotypes for gene: STRADA were changed from Polyhydramnios, megalencephaly, and symptomatic epilepsy, 611087 to Polyhydramnios, megalencephaly, and symptomatic epilepsy, OMIM:611087
Hydrocephalus v2.71 SNX10 Ivone Leong Phenotypes for gene: SNX10 were changed from Osteopetrosis, autosomal recessive 8 to Osteopetrosis, autosomal recessive 8, OMIM:615085
Hydrocephalus v2.70 SKI Ivone Leong Phenotypes for gene: SKI were changed from Shprintzen-Goldberg syndrome to Shprintzen-Goldberg syndrome, OMIM:182212
Hydrocephalus v2.69 RPS6KA3 Ivone Leong Phenotypes for gene: RPS6KA3 were changed from Coffin-Lowry syndrome to Coffin-Lowry syndrome, OMIM:303600
Hydrocephalus v2.68 RNF125 Ivone Leong Phenotypes for gene: RNF125 were changed from Tenorio syndrome to Tenorio syndrome, OMIM:616260
Hydrocephalus v2.67 PTEN Ivone Leong Phenotypes for gene: PTEN were changed from Macrocephaly/autism syndrome to Macrocephaly/autism syndrome, OMIM:605309
Hydrocephalus v2.66 PTCH1 Ivone Leong Phenotypes for gene: PTCH1 were changed from Basal cell nevus syndrome to Basal cell nevus syndrome, OMIM:109400
Hydrocephalus v2.65 PPP2R5D Ivone Leong Phenotypes for gene: PPP2R5D were changed from Mental retardation, autosomal dominant 35 to Mental retardation, autosomal dominant 35, OMIM:616355
Hydrocephalus v2.64 POMT1 Ivone Leong Phenotypes for gene: POMT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1, OMIM:236670
Hydrocephalus v2.63 POMK Ivone Leong Phenotypes for gene: POMK were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12, OMIM:615249
Hydrocephalus v2.62 POMGNT2 Ivone Leong Phenotypes for gene: POMGNT2 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 614830 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8, OMIM:614830
Hydrocephalus v2.61 POMGNT1 Ivone Leong Phenotypes for gene: POMGNT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3, OMIM:253280
Hydrocephalus v2.60 PLG Ivone Leong Phenotypes for gene: PLG were changed from Plasminogen deficiency, type I to Plasminogen deficiency, type I, OMIM:217090
Hydrocephalus v2.59 PIK3R2 Ivone Leong Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 603387 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Hydrocephalus v2.58 PIK3CA Ivone Leong Phenotypes for gene: PIK3CA were changed from Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic 602501 to Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, OMIM:602501
Hydrocephalus v2.57 OSTM1 Ivone Leong Phenotypes for gene: OSTM1 were changed from Osteopetrosis, autosomal recessive 5 259720 to Osteopetrosis, autosomal recessive 5, OMIM:259720
Hydrocephalus v2.56 NSD1 Ivone Leong Phenotypes for gene: NSD1 were changed from Sotos syndrome 1 117550 to Sotos syndrome 1, OMIM:117550
Hydrocephalus v2.55 NF1 Ivone Leong Phenotypes for gene: NF1 were changed from Neurofibromatosis, type 1 to Neurofibromatosis, type 1, OMIM:162200
Hydrocephalus v2.54 MAN2B1 Ivone Leong Phenotypes for gene: MAN2B1 were changed from Mannosidosis, alpha-, types I and II 248500 to Mannosidosis, alpha-, types I and II, OMIM:248500
Hydrocephalus v2.53 LARGE1 Ivone Leong Phenotypes for gene: LARGE1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6 613154 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, OMIM:613154
Hydrocephalus v2.52 LAMB1 Ivone Leong Phenotypes for gene: LAMB1 were changed from Lissencephaly 5 to Lissencephaly 5, OMIM:615191
Hydrocephalus v2.51 L1CAM Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Corpus callosum, partial agenesis of, OMIM:304100;CRASH syndrome, OMIM:303350;Hydrocephalus due to aqueductal stenosis, OMIM:307000;Hydrocephalus with congential idiopathic intestinal pseudoobstruction, OMIM:307000;Hydrocephalus with Hirschsprung disease, OMIM:307000;MASA syndrome, OMIM:303350;X-linked Hydrocephalus with aqueductal stenosis;Hydrocephalus Due To Congenital Stenosis Of Aqueduct Of Sylvius;HSAS
Hydrocephalus v2.51 L1CAM Ivone Leong Phenotypes for gene: L1CAM were changed from Corpus callosum, partial agenesis of; CRASH syndrome; Hydrocephalus due to aqueductal stenosis 307000; Hydrocephalus with congential idiopathic intestinal pseudoobstruction 307000; Hydrocephalus with Hirschsprung disease 307000; MASA syndrome; X-linked Hydrocephalus with aqueductal stenosis; Hydrocephalus Due To Congenital Stenosis Of Aqueduct Of Sylvius; HSAS to Corpus callosum, partial agenesis of, OMIM:304100; CRASH syndrome, OMIM:303350; Hydrocephalus due to aqueductal stenosis, OMIM:307000; Hydrocephalus with congential idiopathic intestinal pseudoobstruction, OMIM:307000; Hydrocephalus with Hirschsprung disease, OMIM:307000; MASA syndrome, OMIM:303350
Hydrocephalus v2.50 KIAA1109 Ivone Leong Phenotypes for gene: KIAA1109 were changed from Alkuraya-Kucinskas syndrome 617822 to Alkuraya-Kucinskas syndrome, OMIM:617822
Hydrocephalus v2.49 KIAA0586 Ivone Leong Phenotypes for gene: KIAA0586 were changed from Short-rib thoracic dysplasia 14 with polydactyly 616546 to Short-rib thoracic dysplasia 14 with polydactyly, OMIM:616546
Hydrocephalus v2.48 ISPD Ivone Leong Phenotypes for gene: ISPD were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, OMIM:614643
Hydrocephalus v2.47 IDS Ivone Leong Phenotypes for gene: IDS were changed from Mucopolysaccharidosis II 309900 to Mucopolysaccharidosis II, OMIM:309900
Hydrocephalus v2.46 HYLS1 Ivone Leong Phenotypes for gene: HYLS1 were changed from Hydrolethalus syndrome 236680 to Hydrolethalus syndrome, OMIM:236680
Hydrocephalus v2.45 HYLS1 Ivone Leong Publications for gene: HYLS1 were set to
Hydrocephalus v2.44 GUSB Ivone Leong Phenotypes for gene: GUSB were changed from Mucopolysaccharidosis VII 253220 to Mucopolysaccharidosis VII, OMIM:253220
Hydrocephalus v2.43 GPSM2 Ivone Leong Phenotypes for gene: GPSM2 were changed from Chudley-McCullough syndrome to Chudley-McCullough syndrome, OMIM:604213
Hydrocephalus v2.42 GLI3 Ivone Leong Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome to Greig cephalopolysyndactyly syndrome, OMIM:175700
Hydrocephalus v2.41 GFAP Ivone Leong Phenotypes for gene: GFAP were changed from Alexander disease 203450 to Alexander disease, OMIM:203450
Hydrocephalus v2.40 FLVCR2 Ivone Leong Phenotypes for gene: FLVCR2 were changed from Proliferative vasculopathy and hydraencephaly-hydrocephaly syndrome 225790 to Proliferative vasculopathy and hydraencephaly-hydrocephaly syndrome, OMIM:225790
Hydrocephalus v2.39 FKTN Ivone Leong Phenotypes for gene: FKTN were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4, OMIM:253800
Hydrocephalus v2.38 FKRP Ivone Leong Phenotypes for gene: FKRP were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, OMIM:613153
Hydrocephalus v2.37 FGFR3 Ivone Leong Phenotypes for gene: FGFR3 were changed from Achondroplasia 100800; Thanatophoric dysplasia 187600; Crouzon syndrome with acanthosis nigricans 612247; Muenke syndrome 602849 to Achondroplasia, OMIM:100800; Thanatophoric dysplasia, OMIM:187600; Crouzon syndrome with acanthosis nigricans, OMIM:612247; Muenke syndrome, OMIM:602849
Hydrocephalus v2.36 FGFR2 Ivone Leong Phenotypes for gene: FGFR2 were changed from Apert syndrome; Crouzon syndrome to Apert syndrome, OMIM:101200; Crouzon syndrome, OMIM:123500
Hydrocephalus v2.35 FGFR1 Ivone Leong Phenotypes for gene: FGFR1 were changed from Pfeiffer syndrome 101600 to Pfeiffer syndrome, OMIM:101600
Hydrocephalus v2.34 FANCB Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
VACTERL Association with Hydrocephalus;Vacterl Association, X-Linked, With Or Without Hydrocephalus, MONDO:0010752;VACTERLX;Fanconi anemia, complementation group B, OMIM:300514
Hydrocephalus v2.34 FANCB Ivone Leong Phenotypes for gene: FANCB were changed from VACTERL Association with Hydrocephalus; Vacterl Association, X-Linked, With Or Without Hydrocephalus; VACTERLX; Fanconi anemia, complementation group B, OMIM:300514 to Vacterl Association, X-Linked, With Or Without Hydrocephalus, MONDO:0010752; Fanconi anemia, complementation group B, OMIM:300514
Hydrocephalus v2.33 FANCB Ivone Leong Phenotypes for gene: FANCB were changed from VACTERL Association with Hydrocephalus; Vacterl Association, X-Linked, With Or Without Hydrocephalus; VACTERLX; Fanconi anemia, complementation group B 300514 to VACTERL Association with Hydrocephalus; Vacterl Association, X-Linked, With Or Without Hydrocephalus; VACTERLX; Fanconi anemia, complementation group B, OMIM:300514
Hydrocephalus v2.32 FAM20C Ivone Leong Phenotypes for gene: FAM20C were changed from Raine syndrome to Raine syndrome, OMIM:259775
Hydrocephalus v2.31 ERF Ivone Leong Phenotypes for gene: ERF were changed from Craniosynostosis 4 600775 to Craniosynostosis 4, OMIM:600775
Hydrocephalus v2.30 EML1 Ivone Leong Phenotypes for gene: EML1 were changed from Band heterotopia, 600348 to Band heterotopia, OMIM:600348
Hydrocephalus v2.29 DHCR24 Ivone Leong Phenotypes for gene: DHCR24 were changed from Desmosterolosis to Desmosterolosis, OMIM:602398
Hydrocephalus v2.28 DENND5A Ivone Leong Phenotypes for gene: DENND5A were changed from Epileptic encephalopathy, early infantile, 49 to Epileptic encephalopathy, early infantile, 49, OMIM:617281
Hydrocephalus v2.27 DAG1 Ivone Leong Phenotypes for gene: DAG1 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9 613818 to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, OMIM:613818
Hydrocephalus v2.26 CRB2 Ivone Leong Phenotypes for gene: CRB2 were changed from Ventriculomegaly with cystic kidney disease 219730 to Ventriculomegaly with cystic kidney disease, OMIM:219730
Hydrocephalus v2.25 COL4A1 Ivone Leong Phenotypes for gene: COL4A1 were changed from Porencephaly 1, OMIM:175780 to Brain small vessel disease with or without ocular anomalies, OMIM:175780
Hydrocephalus v2.24 COL4A1 Ivone Leong Phenotypes for gene: COL4A1 were changed from Porencephaly 1 175780 to Porencephaly 1, OMIM:175780
Hydrocephalus v2.23 CEP83 Ivone Leong Phenotypes for gene: CEP83 were changed from Nephronophthisis 18 615862 to Nephronophthisis 18, OMIM:615862
Severe microcephaly v2.104 PPP1R35 Arina Puzriakova Classified gene: PPP1R35 as Red List (low evidence)
Severe microcephaly v2.104 PPP1R35 Arina Puzriakova Added comment: Comment on list classification: Rating this gene as Red, but with a watchlist tag, until more evidence is available.
Severe microcephaly v2.104 PPP1R35 Arina Puzriakova Gene: ppp1r35 has been classified as Red List (Low Evidence).
Severe microcephaly v2.103 PPP1R35 Arina Puzriakova gene: PPP1R35 was added
gene: PPP1R35 was added to Severe microcephaly. Sources: Other
watchlist tags were added to gene: PPP1R35.
Mode of inheritance for gene: PPP1R35 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PPP1R35 were set to Primary microcephaly
Added comment: Conference poster (Genomics of Rare Disease 2021) - 'Biallelic frameshift indel in PPP1R35 as a cause of primary microcephaly' by Dawood et al, Baylor College of Medicine -

Proband from a Turkish consanguineous family with primary microcephaly (-4.3 SD at birth, -6.1 SD by 42 months) and GDD. Brain imaging showed thinning of corpus collosum, mild cerebellar volume loss, increased extra-axial CSF spaces, pachygyria, dysmorphic ventricular system and delayed myelination of the internal capsule. Exome sequencing revealed a biallelic frameshifting indel in the PPP1R35 gene (c.753_*3delGGAAGCGTAGACCinsCG; p.Trp251Cysfs*22), resulting in deletion of the canonical stop codon in the last exon. Sequencing of unaffected parents and 2 unaffected sibs confirmed segregation with the phenotype. Droplet digital PCR demonstrated expression of mutant mRNA, with comparable gene expression levels observed for mutant and wild-type alleles in fibroblasts.

Authors note a second Iranian consanguineous family in literature with two sibs with microcephaly and the same, p.Trp251Cysfs*22 variant - however, this paper could not be found in PubMed.
Sources: Other
Hydrocephalus v2.22 CENPF Ivone Leong Phenotypes for gene: CENPF were changed from Stromme syndrome 243605 to Stromme syndrome, OMIM:243605
Hydrocephalus v2.21 CCND2 Ivone Leong Phenotypes for gene: CCND2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 615938 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3, OMIM:615938
Hydrocephalus v2.20 CCDC88C Ivone Leong Phenotypes for gene: CCDC88C were changed from Hydrocephalus, nonsyndromic, autosomal recessive 236600 to Hydrocephalus, nonsyndromic, autosomal recessive, OMIM:236600
Hydrocephalus v2.19 CC2D2A Ivone Leong Phenotypes for gene: CC2D2A were changed from Joubert syndrome 9 612285 to Joubert syndrome 9, OMIM:612285
Hydrocephalus v2.18 BUB1B Ivone Leong Phenotypes for gene: BUB1B were changed from Mosaic variegated aneuploidy syndrome 1 257300 to Mosaic variegated aneuploidy syndrome 1, OMIM:257300
Hydrocephalus v2.17 B3GLCT Ivone Leong Phenotypes for gene: B3GLCT were changed from Peters-plus syndrome 261540 to Peters-plus syndrome, OMIM:261540
Hydrocephalus v2.16 B3GALNT2 Ivone Leong Phenotypes for gene: B3GALNT2 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11 615181 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11, OMIM:615181
Hydrocephalus v2.15 ARSB Ivone Leong Phenotypes for gene: ARSB were changed from Mucopolysaccharidosis type VI (Maroteaux-Lamy) 253200; Mucopolysaccharidosis, Type VI to Mucopolysaccharidosis type VI (Maroteaux-Lamy), OMIM:253200
Hydrocephalus v2.14 AP1S2 Ivone Leong Phenotypes for gene: AP1S2 were changed from Mental retardation, X-linked syndromic, OMIM:5 to Mental retardation, X-linked syndromic 5, OMIM:304340
Hydrocephalus v2.13 AP1S2 Ivone Leong Phenotypes for gene: AP1S2 were changed from Mental retardation, X-linked syndromic 5 to Mental retardation, X-linked syndromic, OMIM:5
Hydrocephalus v2.12 AKT3 Ivone Leong Phenotypes for gene: AKT3 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 615937 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, OMIM:615937
Cerebral vascular malformations v2.36 PKD2 Ivone Leong Phenotypes for gene: PKD2 were changed from Polycystic kidney disease 2 613095 to Polycystic kidney disease 2, OMIM:613095
Cerebral vascular malformations v2.35 PKD1 Ivone Leong Phenotypes for gene: PKD1 were changed from Polycystic kidney disease, adult type I 173900 to Polycystic kidney disease, adult type I, OMIM:173900
Cerebral vascular malformations v2.34 PCNT Ivone Leong Phenotypes for gene: PCNT were changed from Moyamoya disease; Microcephalic osteodysplastic primordial dwarfism, type II 210720 to Moyamoya disease, MONDO:0016820; Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Cerebral vascular malformations v2.33 NF1 Ivone Leong Phenotypes for gene: NF1 were changed from Moyamoya disease; Neurofibromatosis, type 1 162200 to Moyamoya disease, MONDO:0016820; Neurofibromatosis, type 1, OMIM:162200
Cerebral vascular malformations v2.32 MYH11 Ivone Leong Phenotypes for gene: MYH11 were changed from moyamoya-like angiopath; Aortic aneurysm, familial thoracic 4, 132900 to moyamoya-like angiopath; Aortic aneurysm, familial thoracic 4, OMIM:132900
Cerebral vascular malformations v2.31 HBB Ivone Leong Phenotypes for gene: HBB were changed from Sickle cell anemia 603903 to Sickle cell anemia, OMIM:603903
Cerebral vascular malformations v2.30 HBB Ivone Leong Phenotypes for gene: HBB were changed from Sickle cell anemia 603903 to Sickle cell anemia 603903
Cerebral vascular malformations v2.29 GDF2 Ivone Leong Phenotypes for gene: GDF2 were changed from to Telangiectasia, hereditary hemorrhagic, type 5, OMIM:615506
Cerebral vascular malformations v2.28 FLVCR2 Ivone Leong Phenotypes for gene: FLVCR2 were changed from Proliferative Vasculopathy And Hydranencephaly-Hydrocephaly Syndrome to Proliferative Vasculopathy And Hydranencephaly-Hydrocephaly Syndrome, OMIM:225790
Cerebral vascular malformations v2.27 EPHB4 Ivone Leong Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2, 618196 to Capillary malformation-arteriovenous malformation 2, OMIM:618196
Cerebral vascular malformations v2.26 CEP152 Ivone Leong Phenotypes for gene: CEP152 were changed from Seckel syndrome 5 613823 to Seckel syndrome 5, OMIM:613823
Cerebral vascular malformations v2.25 CBL Ivone Leong Phenotypes for gene: CBL were changed from early-onset moyamoya angiopathy; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, 613563 to early-onset moyamoya angiopathy; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia, OMIM:613563
Cerebral vascular malformations v2.24 ATR Ivone Leong Phenotypes for gene: ATR were changed from Seckel syndrome 1 210600 to Seckel syndrome 1, OMIM:210600
Cerebral vascular malformations v2.23 ADA2 Ivone Leong Phenotypes for gene: ADA2 were changed from Sneddon syndrome 182410; Polyarteritis nodosa to ?Sneddon syndrome, OMIM:182410; Polyarteritis nodosa, MONDO:0019170
Cerebral vascular malformations v2.22 YY1AP1 Ivone Leong Phenotypes for gene: YY1AP1 were changed from Grange syndrome, 602531 to Grange syndrome, OMIM:602531
Cerebral vascular malformations v2.21 SMAD4 Ivone Leong Phenotypes for gene: SMAD4 were changed from Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome 175050 to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, OMIM:175050
Cerebral vascular malformations v2.20 SLC2A10 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Arterial tortuosity syndrome;Moyamoya disease;208050
Cerebral vascular malformations v2.20 SLC2A10 Ivone Leong Phenotypes for gene: SLC2A10 were changed from Arterial tortuosity syndrome; Moyamoya disease; 208050 to Arterial tortuosity syndrome, OMIM:208050
Cerebral vascular malformations v2.19 SAMHD1 Ivone Leong Phenotypes for gene: SAMHD1 were changed from Moyamoya disease to Moyamoya disease, MONDO:0016820
Cerebral vascular malformations v2.18 RNF213 Ivone Leong Phenotypes for gene: RNF213 were changed from {Moyamoya disease 2, susceptibility to} to {Moyamoya disease 2, susceptibility to}, OMIM:607151
Cerebral vascular malformations v2.17 RASA1 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Capillary malformation-arteriovenous malformation 1, OMIM:608354;Parkes Weber syndrome, 608355;Parkes Weber syndrome (PKWS);Capillary Malformation-Arteriovenous Malformation Syndrome;Parkes Weber Syndrome;Parkes Weber syndrome
Cerebral vascular malformations v2.17 RASA1 Ivone Leong Phenotypes for gene: RASA1 were changed from Capillary malformation-arteriovenous malformation, 608354; Parkes Weber syndrome, 608355; Parkes Weber syndrome (PKWS); Capillary Malformation-Arteriovenous Malformation Syndrome; Parkes Weber Syndrome; Parkes Weber syndrome to Capillary malformation-arteriovenous malformation 1, OMIM:608354
Cerebral vascular malformations v2.16 PDCD10 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Cerebral cavernous malformations 3, 603285;Cerebral Cavernous Malformation;Cerebral cavernous malformations 3;Cerebral Cavernous Malformations;Familial Cerebral Cavernous Malformation
Cerebral vascular malformations v2.16 PDCD10 Ivone Leong Phenotypes for gene: PDCD10 were changed from Cerebral cavernous malformations 3, 603285; Cerebral Cavernous Malformation; Cerebral cavernous malformations 3; Cerebral Cavernous Malformations; Familial Cerebral Cavernous Malformation to Cerebral cavernous malformations 3, OMIM:603285
Cerebral vascular malformations v2.15 KRIT1 Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes:
Cerebral cavernous malformations-1, 116860 ;Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations, 116860;Cerebral Cavernous Malformation;Cerebral cavernous malformations 1 ;Cerebral Cavernous Malformations;Familial Cerebral Cavernous Malformation;Angiokeratoma Corporis Diffusum with Arteriovenous Fistulas
Cerebral vascular malformations v2.15 KRIT1 Ivone Leong Phenotypes for gene: KRIT1 were changed from Cerebral cavernous malformations-1, 116860 ; Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations, 116860; Cerebral Cavernous Malformation; Cerebral cavernous malformations 1 ; Cerebral Cavernous Malformations; Familial Cerebral Cavernous Malformation; Angiokeratoma Corporis Diffusum with Arteriovenous Fistulas to Cerebral cavernous malformations-1, OMIM:116860; Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations, OMIM:116860; Cavernous malformations of CNS and retina, OMIM:116860
Cerebral vascular malformations v2.14 GUCY1A3 Ivone Leong Phenotypes for gene: GUCY1A3 were changed from Moyamoya 6 with achalasia; Moyamoya 6 with achalasia, 615750 to Moyamoya 6 with achalasia, OMIM:615750
Cerebral vascular malformations v2.13 ENG Ivone Leong Phenotypes for gene: ENG were changed from Telangiectasia, hereditary hemorrhagic, type 1 187300 to Telangiectasia, hereditary hemorrhagic, type 1, OMIM:187300
Cerebral vascular malformations v2.12 COL3A1 Ivone Leong Phenotypes for gene: COL3A1 were changed from Ehlers-Danlos syndrome, type IV 130050 to Ehlers-Danlos syndrome, vascular type, OMIM:130050
Cerebral vascular malformations v2.11 CCM2 Ivone Leong Phenotypes for gene: CCM2 were changed from Cerebral cavernous malformations-2 603284; Capillary malformation-arteriovenous malformation 608354 to Cerebral cavernous malformations-2, OMIM:603284
Cerebral vascular malformations v2.10 ACVRL1 Ivone Leong Phenotypes for gene: ACVRL1 were changed from Telangiectasia, hereditary hemorrhagic, type 2 600376 to Telangiectasia, hereditary hemorrhagic, type 2, OMIM; 600376
Cerebral vascular malformations v2.9 ACTA2 Ivone Leong Added comment: Comment on phenotypes: This gene is also associated with Aortic aneurysm familial thoracic 6,611788; Multisystemic smooth muscle dysfunction syndrome,613834