Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV002467003 | SCV002762031 | pathogenic | not provided | 2022-06-09 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation, as the last 1580 amino acids are replaced with 4 different amino acids, and other loss-of-function variants have been reported downstream in HGMD |
| Victorian Clinical Genetics Services, |
RCV002471295 | SCV002766728 | pathogenic | Intellectual developmental disorder, autosomal dominant 64 | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. (I) 0107 - This gene is associated with autosomal dominant disease. To date, only heterozygous variants have been reported to cause disease in this gene (DECIPHER, PMID: 31723249). (I) 0204 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with at least 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0600 - Variant is located upstream of multiple annotated zinc finger motifs (NCBI, UniProt). (I) 0701 - Other truncating variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. More than fifteen downstream truncating variants have previously been reported as pathogenic in individuals with ZNF292-related neurodevelopmental disorder (DECIPHER, PMID: 31723249). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |