Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002018720 | SCV002259932 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-07-24 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 affected with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with lysine at codon 1713 of the BRCA2 protein (p.Asn1713Lys). The asparagine residue is moderately conserved and there is a moderate physicochemical difference between asparagine and lysine. |
University of Washington Department of Laboratory Medicine, |
RCV003156956 | SCV003847021 | 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 | RCV003156956 | SCV005097549 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-25 | criteria provided, single submitter | clinical testing | The p.N1713K variant (also known as c.5139T>G), located in coding exon 10 of the BRCA2 gene, results from a T to G substitution at nucleotide position 5139. The asparagine at codon 1713 is replaced by lysine, 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. Based on the available evidence, the clinical significance of this variant remains unclear. |