Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002471317 | SCV002767208 | likely pathogenic | Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies | 2020-10-19 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with cleft palate, cardiac defects, and intellectual disability (MIM#600987). Dominant negative has been suggested as a potential mechanism of disease for missense variants (PMID: 30055086, PMID: 30291340). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from asparagine to serine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). This residue is a specific DNA base contact within the homeobox KN domain (NCBI, DECIPHER, PDB). (SP) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. The alternative change p.(Asn329Ser) has been reported as likely pathogenic (ClinVar). (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) 1102 - Strong phenotype match for this individual. (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |