Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000476388 | SCV000549740 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-12-16 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 2498 of the BRCA2 protein (p.Lys2498Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 156173). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA2 protein function. 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. |
| Counsyl | RCV000144190 | SCV000785267 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-06-27 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002390301 | SCV002669821 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-23 | criteria provided, single submitter | clinical testing | The p.K2498T variant (also known as c.7493A>C), located in coding exon 14 of the BRCA2 gene, results from an A to C substitution at nucleotide position 7493. The lysine at codon 2498 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV004567161 | SCV005058348 | uncertain significance | Familial cancer of breast | 2024-03-26 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998290 | SCV005625287 | uncertain significance | not provided | 2023-10-24 | criteria provided, single submitter | clinical testing | The BRCA2 c.7493A>C (p.Lys2498Thr) variant has been reported in the published literature in an individual with breast cancer (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/BRCA2)).This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Sharing Clinical Reports Project |
RCV000144190 | SCV000189263 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2011-05-13 | no assertion criteria provided | clinical testing |