Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564446 | SCV000665358 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-10 | criteria provided, single submitter | clinical testing | The p.R3276S variant (also known as c.9828A>T), located in coding exon 26 of the BRCA2 gene, results from an A to T substitution at nucleotide position 9828. The arginine at codon 3276 is replaced by serine, an amino acid with dissimilar properties. This alteration was identified in the control population of a study looking for BRCA2 variants in breast and breast/ovarian cancer families (Wagner TM et al. Hum. Mol. Genet. 1999 Mar;8:413-23). This amino acid position is highly conserved through mammals but not in all 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. |
| Color Diagnostics, |
RCV000564446 | SCV001350583 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-21 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001857382 | SCV002276941 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 3276 of the BRCA2 protein (p.Arg3276Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 32438681). ClinVar contains an entry for this variant (Variation ID: 52904). 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. |
| Breast Cancer Information Core |
RCV000112815 | SCV000145717 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 1998-11-30 | no assertion criteria provided | clinical testing |