Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004522714 | SCV005030529 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-03 | criteria provided, single submitter | clinical testing | The p.T2681P variant (also known as c.8041A>C), located in coding exon 17 of the BRCA2 gene, results from an A to C substitution at nucleotide position 8041. The threonine at codon 2681 is replaced by proline, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
| Labcorp Genetics |
RCV005100648 | SCV005734709 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-11-04 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 2681 of the BRCA2 protein (p.Thr2681Pro). 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: 3229091). 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. |