Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002419230 | SCV002678693 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-19 | criteria provided, single submitter | clinical testing | The p.A2671T variant (also known as c.8011G>A), located in coding exon 17 of the BRCA2 gene, results from a G to A substitution at nucleotide position 8011. The alanine at codon 2671 is replaced by threonine, an amino acid with similar properties. This variant was identified in 1 of 7051 unselected female breast cancer patients, 6 of 11241 female controls of Japanese ancestry, 2 of 7636 unselected prostate cancer patients, and 0 of 12366 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 Oct;9:4083; Momozawa Y et al. J Natl Cancer Inst, 2020 Apr;112:369-376). In an assay testing homologous recombination function, this variant showed a functionally normal result. (Guo Q et al. J Hum Genet, 2023 Dec;68:849-857). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV003645303 | SCV004551703 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2671 of the BRCA2 protein (p.Ala2671Thr). 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: 1761657). 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. |