Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002471756 | SCV002766664 | pathogenic | Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0204 - Variant is predicted to result in a truncated protein with more than 1/3 of the protein affected (exon 17 of 17). (P) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0401 - Variant is located in a gene associated with a severe early-onset dominant condition that is intolerant to loss-of-function variants. (P) 0601 - Variant affects at least one well-established (essential) functional domain or motif. The variant is located within the transactivation domain which is essential for normal protein function (PMID: 25728777). (P) 0701 - Comparable variants have very strong previous evidence for pathogenicity. Other variants predicted to cause a truncated protein have been reported as pathogenic in ClinVar. (P) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1204 - Variant shown to be de novo in proband (parental status not tested but assumed). (P) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |