Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of Molecular Epidemiology of Birth Defects, |
RCV003154730 | SCV003843571 | benign | Ovarian cancer | 2022-01-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003530281 | SCV004253612 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 3182 of the BRCA2 protein (p.His3182Pro). 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: 2445320). 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 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 | RCV004246185 | SCV005032045 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-18 | criteria provided, single submitter | clinical testing | The p.H3182P variant (also known as c.9545A>C), located in coding exon 25 of the BRCA2 gene, results from an A to C substitution at nucleotide position 9545. The histidine at codon 3182 is replaced by proline, an amino acid with similar properties. This alteration was identified in a cohort of 882 Chinese individuals with a personal and/or family history of breast or ovarian cancers who underwent multi-gene panel testing for HBOC risk assessment (Shao D et al. Cancer Sci, 2020 Feb;111:647-657). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |