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| Mendeliome v1.2496 | BEAN1_SCA31_TGGAA | Bryony Thompson SCA31 was changed to BEAN1_SCA31_TGGAA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1973 | REPS2 |
Mark Cleghorn gene: REPS2 was added gene: REPS2 was added to Mendeliome. Sources: Other Mode of inheritance for gene: REPS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: REPS2 were set to complex neurodevelopmental disorder MONDO:0100038; Cerebral palsy HP:0100021 Penetrance for gene: REPS2 were set to unknown Review for gene: REPS2 was set to AMBER Added comment: REPS2 Hao Hu, Guangzhou Women and Children’s MC ESHG talk 1/6/24, unpublished Proposed X-linked cerebral palsy + NDD gene 4 unrelated males with predicted deleterious hemizygous REPS2 variants, 2 PTC, 2 missense. 2 de novo, 2 maternally inherited Phenotypes: 2 w CP + moderate ID/ASD, 2 w NDD NOS Variants described: c.1050_1052delGAA;p.K351del c.1040T>C; p.I347T c.962C>G; p.S321C c.1736delA; p.N579Tfs*17 In vitro assay of above 4 variants suggest reduced REPS2 protein stability Zebrafish model: REPS2 expressed in neuronal cells, REPS2 knock down have reduced motor activity and abN neuronal morphology Mouse model hemizygous w one of above variants (not specified): reduced performance in cognitive tasks, abnormal neuronal migration pattern on post mortem examination Mechanism may relate to dopamine signalling? Sources: Other |
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| Mendeliome v1.691 | HMGB1 |
Ain Roesley edited their review of gene: HMGB1: Added comment: PMID:36755093 4 new families with de novo protein truncating variants. In addition with PMID 34159400 ( all de novos) c.556_559delGAAG;p.(Glu186Argfs*42) - 1 family c.551_554delAGAA;p.(Lys184Argfs*44) - 4 families; Changed rating: GREEN; Changed publications: 34159400, 36755093; Changed phenotypes: brachyphalangy, polydactyly, and tibial aplasia/hypoplasia MIM#163905; Set current diagnostic: yes |
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| Mendeliome v0.14223 | FXN | Bryony Thompson edited their review of gene: FXN: Added comment: Well-established gene-disease association. 96% of cases are caused by biallelic intronic GAA triplet repeat expansion and 4% are attributable to biallelic single nucleotide variants and small indels. Loss of function is the mechanism of disease.; Changed rating: GREEN; Changed publications: 20301458, 26704351; Changed phenotypes: Friedreich ataxia MONDO:0100339; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Set current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8972 | FAME1 |
Bryony Thompson STR: FAME1 was added STR: FAME1 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: FAME1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for STR: FAME1 were set to 30194086; 29507423 Phenotypes for STR: FAME1 were set to Epilepsy, familial adult myoclonic, 1 MIM#601068 Review for STR: FAME1 was set to GREEN STR: FAME1 was marked as clinically relevant Added comment: NC_000008.10:g.119379055_119379157TGAAA[X]TAAAA[X] A heterozygous or homozygous 5-bp expanded TTTCA(n) insertion associated with an upstream 5-bp TTTTA(n) repeat expansion in a noncoding region within intron 4 of the SAMD12 gene, was identified in over 50 Chinese and Japanese families. 4 homozygous cases from 3 families had a more severe phenotype. The TTTTA repeat was present in controls, while the TTTCA was absent and only present in cases (100-3680 repeats reported). RNA toxicity is expected to be the mechanism of disease. Sources: Expert list |
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| Mendeliome v0.7066 | GAA | Zornitza Stark Phenotypes for gene: GAA were changed from Glycogen storage disease II, MIM# 232300 to Glycogen storage disease II, MIM# 232300; MONDO:0009290 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.6825 | SCA31 |
Bryony Thompson STR: SCA31 was added STR: SCA31 was added to Mendeliome. Sources: Expert list Mode of inheritance for STR: SCA31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: SCA31 were set to 19878914; 31755042 Phenotypes for STR: SCA31 were set to Spinocerebellar ataxia 31 MIM#117210 Review for STR: SCA31 was set to GREEN STR: SCA31 was marked as clinically relevant Added comment: Complex repeat insertion (TGGAA)n, (TAGAA)n, (TAAAA)n, (TAAAATAGAA)n, TGGAA is present only in affected cases. Sequencing showed that the insertion consisted of a preceding TCAC sequence, and 3 pentanucleotide repeat components (TGGAA)n, (TAGAA)n, and (TAAAA)n in all patients tested. 2.5-3.8 KB insertion is associated with disease and RNA toxicity expected to be mechanism of disease Normal and pathogenic cut-offs are based on animal model experiments (PMID: 31755042) Sources: Expert list |
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| Mendeliome v0.2872 | GAA | Zornitza Stark Marked gene: GAA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2872 | GAA | Zornitza Stark Gene: gaa has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2872 | GAA | Zornitza Stark Phenotypes for gene: GAA were changed from to Glycogen storage disease II, MIM# 232300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2871 | GAA | Zornitza Stark Mode of inheritance for gene: GAA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2861 | GAA | Elena Savva reviewed gene: GAA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glycogen storage disease II 232300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.0 | GAA |
Zornitza Stark gene: GAA was added gene: GAA was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: GAA was set to Unknown |
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