Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002695553 | SCV002994488 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-01-13 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1026 of the BRCA2 protein (p.Lys1026Asn). 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 affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). |
University of Washington Department of Laboratory Medicine, |
RCV003157222 | SCV003850366 | 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 | RCV003157222 | SCV005552012 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-09 | criteria provided, single submitter | clinical testing | The p.K1026N variant (also known as c.3078G>C), located in coding exon 10 of the BRCA2 gene, results from a G to C substitution at nucleotide position 3078. The lysine at codon 1026 is replaced by asparagine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |