Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000801480 | SCV000941257 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-12-16 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with proline at codon 2825 of the BRCA2 protein (p.Ala2825Pro). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 | RCV001017858 | SCV001179017 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-30 | criteria provided, single submitter | clinical testing | The p.A2825P variant (also known as c.8473G>C), located in coding exon 18 of the BRCA2 gene, results from a G to C substitution at nucleotide position 8473. The alanine at codon 2825 is replaced by proline, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. 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. |