Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001296693 | SCV001485664 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-09-02 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. 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 lysine with asparagine at codon 972 of the BRCA2 protein (p.Lys972Asn). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and asparagine. |
University of Washington Department of Laboratory Medicine, |
RCV003158663 | SCV003850231 | 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). |
Ambry Genetics | RCV003158663 | SCV005025741 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-14 | criteria provided, single submitter | clinical testing | The p.K972N variant (also known as c.2916A>C), located in coding exon 10 of the BRCA2 gene, results from an A to C substitution at nucleotide position 2916. The lysine at codon 972 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. 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. |