Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000165319 | SCV000216041 | likely benign | Hereditary cancer-predisposing syndrome | 2020-02-12 | 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. |
Gene |
RCV001551664 | SCV001772222 | uncertain significance | not provided | 2017-06-26 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function |
Labcorp Genetics |
RCV001850315 | SCV002255316 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-06-29 | criteria provided, single submitter | clinical testing | 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 expected to disrupt BRCA2 protein function. This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 185825). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 2827 of the BRCA2 protein (p.Pro2827Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. |
All of Us Research Program, |
RCV004804747 | SCV005425799 | uncertain significance | BRCA2-related cancer predisposition | 2024-05-09 | criteria provided, single submitter | clinical testing |