Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000574644 | SCV000666136 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-31 | criteria provided, single submitter | clinical testing | The p.P3311S variant (also known as c.9931C>T), located in coding exon 26 of the BRCA2 gene, results from a C to T substitution at nucleotide position 9931. The proline at codon 3311 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001367217 | SCV001563561 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-11-09 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 3311 of the BRCA2 protein (p.Pro3311Ser). 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: 481595). 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. |
| Baylor Genetics | RCV003459321 | SCV004216019 | uncertain significance | Familial cancer of breast | 2023-12-06 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004820058 | SCV005441041 | uncertain significance | not provided | 2024-06-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates 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 10159C>T; This variant is associated with the following publications: (PMID: 29884841, 10733923) |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004820058 | SCV005625365 | uncertain significance | not provided | 2024-06-26 | criteria provided, single submitter | clinical testing | The BRCA2 c.9931C>T (p.Pro3311Ser) variant has been reported in the published literature to be located in a region of the BRCA2 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). To the best of our knowledge, this variant has not been reported in individuals with BRCA2-related disorders. This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |