Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001022552 | SCV001184304 | likely benign | Hereditary cancer-predisposing syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Color Diagnostics, |
RCV001022552 | SCV001345655 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001873361 | SCV002269544 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-11-25 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1494 of the BRCA2 protein (p.Ser1494Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 824925). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Gene |
RCV002281148 | SCV002569520 | uncertain significance | not provided | 2022-03-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 4708A>G |
| University of Washington Department of Laboratory Medicine, |
RCV001022552 | SCV003850541 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |