Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000204787 | SCV000261634 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-05-20 | 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. ClinVar contains an entry for this variant (Variation ID: 220790). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 2882 of the BRCA2 protein (p.Lys2882Asn). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and asparagine. |
| Ambry Genetics | RCV004601130 | SCV005097498 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-24 | criteria provided, single submitter | clinical testing | The p.K2882N variant (also known as c.8646A>T), located in coding exon 20 of the BRCA2 gene, results from an A to T substitution at nucleotide position 8646. The lysine at codon 2882 is replaced by asparagine, an amino acid with similar 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. Based on the available evidence, the clinical significance of this variant remains unclear. |