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| DDG2P v3.12 | STS | Achchuthan Shanmugasundram reviewed gene: STS: Rating: GREEN; Mode of pathogenicity: ; Publications: 1539590, 9252398, 3032454; Phenotypes: ICHTHYOSIS, X-LINKED, OMIM:308100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | STN1 | Achchuthan Shanmugasundram reviewed gene: STN1: Rating: GREEN; Mode of pathogenicity: ; Publications: 27432940; Phenotypes: Cerebroretinal microangiopathy with calcifications and cysts 2, OMIM:617341; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | SNORD118 | Achchuthan Shanmugasundram reviewed gene: SNORD118: Rating: GREEN; Mode of pathogenicity: ; Publications: 27793341, 27571260; Phenotypes: Leukoencephalopathy with cerebral calcification & cysts, OMIM:614561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | MLC1 | Achchuthan Shanmugasundram reviewed gene: MLC1: Rating: GREEN; Mode of pathogenicity: ; Publications: 11935341, 11254442, 12189496, 21624973, 14615938; Phenotypes: LEUKOENCEPHALOPATHY MEGALENCEPHALIC WITH SUBCORTICAL CYSTS, OMIM:604004; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | LAMA1 | Achchuthan Shanmugasundram reviewed gene: LAMA1: Rating: GREEN; Mode of pathogenicity: ; Publications: 21937992, 25105227; Phenotypes: CEREBELLAR DYSPLASIA WITH CYSTS WITH OR WITHOUT RETINAL DYSTROPHY, OMIM:615960; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | HNF1B | Achchuthan Shanmugasundram reviewed gene: HNF1B: Rating: GREEN; Mode of pathogenicity: ; Publications: 11085914, 9398836, 11562418, 17440011, 15181075, 10484768, 10720943, 15068978, 12675839, 11317673; Phenotypes: RENAL CYSTS AND DIABETES SYNDROME, OMIM:137920; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.12 | CTC1 | Achchuthan Shanmugasundram reviewed gene: CTC1: Rating: GREEN; Mode of pathogenicity: ; Publications: 22267198, 22387016; Phenotypes: CEREBRORETINAL MICROANGIOPATHY WITH CALCIFICATIONS AND CYSTS, OMIM:612199; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.11 | STS | Achchuthan Shanmugasundram Publications for gene: STS were updated from 3032454; 9252398; 1539590 to 1539590; 9252398; 3032454 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v3.6 | AMOTL1 |
Irina Ziravecka edited their review of gene: AMOTL1: Added comment: PMID: 36751037 - this cohort suggests that heterozygous missense variants in AMOTL1, most commonly affecting amino acid residues 157–161, define a new orofacial clefting syndrome, and indicates an important functional role for this undefined region. 5 out of 16 patients in this cohort have developmental delay.; Changed phenotypes to: orofacial clefting, cardiac anomalies, tall stature, distinct dysmorphisms (abnormal head shape, craniosynostosis, hypertelorism, and large ears), myopia, hearing loss, micrognathia, immune dysfunction, scoliosis, chronic constipation, liver dysfunction, global developmental delay |
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| DDG2P v3.6 | AMOTL1 |
Irina Ziravecka changed review comment from: PMID: 36751037 - this cohort suggests that heterozygous missense variants in AMOTL1, most commonly affecting amino acid residues 157–161, define a new orofacial clefting syndrome, and indicates an important functional role for this undefined region. Sources: Other; to: PMID: 36751037 - this cohort suggests that heterozygous missense variants in AMOTL1, most commonly affecting amino acid residues 157–161, define a new orofacial clefting syndrome, and indicates an important functional role for this undefined region. 5 out of 16 patients in this cohort have developmental delay. |
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| DDG2P v3.6 | AMOTL1 |
Irina Ziravecka gene: AMOTL1 was added gene: AMOTL1 was added to DDG2P. Sources: Other Mode of inheritance for gene: AMOTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AMOTL1 were set to PMID: 36751037 Phenotypes for gene: AMOTL1 were set to orofacial clefting; cardiac anomalies; tall stature Mode of pathogenicity for gene: AMOTL1 was set to Other Review for gene: AMOTL1 was set to GREEN Added comment: PMID: 36751037 - this cohort suggests that heterozygous missense variants in AMOTL1, most commonly affecting amino acid residues 157–161, define a new orofacial clefting syndrome, and indicates an important functional role for this undefined region. Sources: Other |
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| DDG2P v2.50 | TAF4 |
Dmitrijs Rots gene: TAF4 was added gene: TAF4 was added to DDG2P. Sources: Literature Mode of inheritance for gene: TAF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TAF4 were set to 33875846 Phenotypes for gene: TAF4 were set to Developmental delay Penetrance for gene: TAF4 were set to unknown Review for gene: TAF4 was set to GREEN Added comment: From the literature: "A heterozygous de novo variant (frameshift) was reported in TAF4 by Kosmicki et al., in a patient with autism.36 The gene has no phenotypic association in OMIM (accessed 12 October 2020). Within this study, we identified two additional de novo LoF variants (splicing and nonsense) in two unrelated patients with dysmorphic features and NDD. TAF4 is highly intolerant to LoF as documented in gnomAD (pLi = 1). Expression of TAF4 varies during development and in the processes of cell differentiation; TAF4 is detected in various regions of the human brain, and it is believed to control the differentiation of human neural progenitor cells having a role in the regulation of neural development and brain function.37 The current data suggests that TAF4 haploinsufficiency leads to NDD in humans." Sources: Literature |
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| DDG2P v2.46 | ALG8 | Sarah Leigh Added comment: Comment on mode of inheritance: Monoallelic variants are associated with Polycystic liver disease 3 with or without kidney cysts OMIM:617874, which is not relevant to this panel. Therefore biallelic moi is relevant to this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.127 | SNORD118 | Rebecca Foulger Phenotypes for gene: SNORD118 were changed from Leukoencephalopathy with cerebral calcification & cysts to Leukoencephalopathy with cerebral calcification & cysts 614561 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.126 | SNORD118 | Rebecca Foulger changed review comment from: Original DDG2P rating: both DD and IF. ; to: Original DDG2P rating for Leukoencephalopathy with cerebral calcification & cysts: both DD and IF. DDG2P Mutation consequence: loss of function; DDG2P allelic requirement: biallelic. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.126 | SNORD118 | Rebecca Foulger commented on gene: SNORD118: In a Gene2Phenotype update (September 2019) the G2P confidence rating of 'both DD and IF' was changed to 'both RD and IF' (where RD = relevant disease and IF = incidental disorder). Therefore the rating is now 'both RD and IF' for Leukoencephalopathy with cerebral calcification & cysts. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.95 | LAMA1 | Rebecca Foulger Phenotypes for gene: LAMA1 were changed from CEREBELLAR DYSPLASIA WITH CYSTS WITH OR WITHOUT RETINAL DYSTROPHY; AUTOSOMAL RECESSIVE MENTAL RETARDATION to CEREBELLAR DYSPLASIA WITH CYSTS WITH OR WITHOUT RETINAL DYSTROPHY 615960; AUTOSOMAL RECESSIVE MENTAL RETARDATION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.56 | LRP5 | Rebecca Foulger Added comment: Comment on mode of inheritance: DDG2P lists MOI as monoallelic for ENDOSTEAL HYPEROSTOSIS WORTH TYPE; monoallelic for HIGH BONE MASS TRAIT; monoallelic for OSTEOPETROSIS AUTOSOMAL DOMINANT TYPE 1; biallelic for OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME; monoallelic for VITREORETINOPATHY EXUDATIVE TYPE 4. All diseases have a confirmed Disease confidence rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.25 | NFIB | Rebecca Foulger commented on gene: NFIB: New gene:disorder association added to DDG2P in March 2019: Intellectual Disability and Macrocephaly. DDG2P Disease confidence: probable. DDG2P mode of pathogenicity/mutation consequence: loss of function. DDG2P mode of inheritance: monoallelic. Note that at the time of curation, the existing disorder 'Intellectual Disability and macrocephaly' exists in DD-G2P as a separate entry. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v1.14 | COG4 | Rebecca Foulger commented on gene: COG4: New gene:disorder association added to DDG2P in March 2019: Saul-Wilson syndrome. DDG2P Disease confidence: probable. DDG2P mode of pathogenicity/mutation consequence: all missense/in frame. DDG2P mode of inheritance: monoallelic. (Note that Saul-Wilson syndrome disorder was already associated with COG4 in DD-G2P but with a 'gain of function' MOP. The new entry exists in addition). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v0.95 | SNORD118 | Rebecca Foulger commented on gene: SNORD118: Changed rating to Amber to reflect DDG2P Disease confidence of 'DD and IF' for Leukoencephalopathy with cerebral calcification & cysts. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v0.2 | STS | Rebecca Foulger reviewed gene: STS: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DDG2P v0.1 | STS |
Rebecca Foulger gene: STS was added gene: STS was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: STS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: STS were set to 3032454; 9252398; 1539590 Phenotypes for gene: STS were set to ICHTHYOSIS, X-LINKED 308100 |
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| DDG2P v0.1 | STN1 |
Rebecca Foulger gene: STN1 was added gene: STN1 was added to DDG2P. Sources: Expert Review Amber,DD-Gene2Phenotype Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STN1 were set to 27432940 Phenotypes for gene: STN1 were set to Cerebroretinal microangiopathy with calcifications and cysts 2 |
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| DDG2P v0.1 | SNORD118 |
Rebecca Foulger gene: SNORD118 was added gene: SNORD118 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: SNORD118 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SNORD118 were set to 27793341; 27571260 Phenotypes for gene: SNORD118 were set to Leukoencephalopathy with cerebral calcification & cysts |
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| DDG2P v0.1 | MLC1 |
Rebecca Foulger gene: MLC1 was added gene: MLC1 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: MLC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MLC1 were set to 11254442; 12189496; 14615938; 11935341; 21624973 Phenotypes for gene: MLC1 were set to LEUKOENCEPHALOPATHY MEGALENCEPHALIC WITH SUBCORTICAL CYSTS 604004 |
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| DDG2P v0.1 | LAMA1 |
Rebecca Foulger gene: LAMA1 was added gene: LAMA1 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: LAMA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LAMA1 were set to 25105227 Phenotypes for gene: LAMA1 were set to CEREBELLAR DYSPLASIA WITH CYSTS WITH OR WITHOUT RETINAL DYSTROPHY |
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| DDG2P v0.1 | HNF1B |
Rebecca Foulger gene: HNF1B was added gene: HNF1B was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: HNF1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: HNF1B were set to 9398836; 11085914; 10484768; 15068978; 17440011; 11562418; 11317673; 10720943; 12675839; 15181075 Phenotypes for gene: HNF1B were set to RENAL CYSTS AND DIABETES SYNDROME 137920 |
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| DDG2P v0.1 | CTC1 |
Rebecca Foulger gene: CTC1 was added gene: CTC1 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype Mode of inheritance for gene: CTC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CTC1 were set to 22267198; 22387016 Phenotypes for gene: CTC1 were set to CEREBRORETINAL MICROANGIOPATHY WITH CALCIFICATIONS AND CYSTS 612199 |
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