Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001207442 | SCV001378797 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-08-05 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with serine at codon 2473 of the BRCA2 protein (p.Cys2473Ser). The cysteine residue is weakly conserved and there is a moderate physicochemical difference between cysteine and serine. |
| Ambry Genetics | RCV002379788 | SCV002668369 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-28 | criteria provided, single submitter | clinical testing | The p.C2473S variant (also known as c.7417T>A), located in coding exon 13 of the BRCA2 gene, results from a T to A substitution at nucleotide position 7417. The cysteine at codon 2473 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is not well 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. |