Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001231010 | SCV001403513 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-10-02 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with BRCA2-related conditions. 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 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"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glutamic acid at codon 2161 of the BRCA2 protein (p.Asp2161Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. |
Ambry Genetics | RCV002356992 | SCV002654827 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-15 | criteria provided, single submitter | clinical testing | The p.D2161E variant (also known as c.6483C>A), located in coding exon 10 of the BRCA2 gene, results from a C to A substitution at nucleotide position 6483. The aspartic acid at codon 2161 is replaced by glutamic acid, an amino acid with highly 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
University of Washington Department of Laboratory Medicine, |
RCV002356992 | SCV003852573 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |