Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588196 | SCV000695275 | uncertain significance | not provided | 2017-03-03 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA2 c.9839C>G (p.Pro3280Arg) variant involves the alteration of a conserved nucleotide. The variant is not found within a known functional domain of the protein (InterPro). 5/5 in silico tools predict a damaging outcome for this variant. This variant is absent from the large control population database ExAC (0/121382 control chromosomes). To our knowledge, the variant of interest has not been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available. |
| Labcorp Genetics |
RCV000704666 | SCV000833622 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2025-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 3280 of the BRCA2 protein (p.Pro3280Arg). 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: 495523). 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. |
| Ambry Genetics | RCV002384281 | SCV002693189 | likely benign | Hereditary cancer-predisposing syndrome | 2020-08-21 | 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. |
| Center for Genomic Medicine, |
RCV003321691 | SCV004027494 | uncertain significance | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing |