Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000809027 | SCV000949163 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 3267 of the BRCA2 protein (p.Lys3267Asn). 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: 653282). 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. 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 | RCV001019786 | SCV001181190 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-28 | criteria provided, single submitter | clinical testing | The p.K3267N variant (also known as c.9801G>C), located in coding exon 26 of the BRCA2 gene, results from a G to C substitution at nucleotide position 9801. The lysine at codon 3267 is replaced by asparagine, an amino acid with similar properties. This amino acid position is highly 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. |
| Baylor Genetics | RCV004569654 | SCV005059023 | uncertain significance | Familial cancer of breast | 2024-02-28 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004723221 | SCV005338017 | uncertain significance | BRCA2-related disorder | 2024-08-14 | no assertion criteria provided | clinical testing | The BRCA2 c.9801G>C variant is predicted to result in the amino acid substitution p.Lys3267Asn. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. This variant is interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/653282/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |