Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998148 | SCV000600592 | uncertain significance | not provided | 2024-04-15 | criteria provided, single submitter | clinical testing | The BRCA2 c.4537G>A (p.Asp1513Asn) variant has been reported in the published literature in a cohort of hereditary breast/ovarian (HBOC) families and reportedly healthy individuals (PMID: 9971877 (1999)), and described to be located in a region of the BRCA2 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). 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 benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Color Diagnostics, |
RCV000773264 | SCV000906911 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-01 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with asparagine at codon 1513 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV001367592 | SCV001563947 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-09-15 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 10923033, 21520333). 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. ClinVar contains an entry for this variant (Variation ID: 51664). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with asparagine at codon 1513 of the BRCA2 protein (p.Asp1513Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. |
| University of Washington Department of Laboratory Medicine, |
RCV000773264 | SCV003850588 | 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). |
| Breast Cancer Information Core |
RCV000113315 | SCV000146441 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 1998-11-30 | no assertion criteria provided | clinical testing |