Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001759214 | SCV002006933 | uncertain significance | not provided | 2020-08-25 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 2740A>G |
University of Washington Department of Laboratory Medicine, |
RCV003158929 | SCV003848375 | 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). |
Labcorp Genetics |
RCV003530206 | SCV004325540 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-09-21 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1317342). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (rs747578057, gnomAD 0.007%). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 838 of the BRCA2 protein (p.Lys838Glu). |