Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000217666 | SCV000273327 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-22 | criteria provided, single submitter | clinical testing | The p.N2425D variant (also known as c.7273A>G and c.7501A>G), located in coding exon 13 of the BRCA2 gene, results from an A to G substitution at nucleotide position 7273. The asparagine at codon 2425 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |
Color Diagnostics, |
RCV000217666 | SCV000905835 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-31 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001344077 | SCV001538106 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-09-20 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 229947). 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). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 2425 of the BRCA2 protein (p.Asn2425Asp). 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. 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. |
All of Us Research Program, |
RCV004804865 | SCV005424580 | uncertain significance | BRCA2-related cancer predisposition | 2024-05-14 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with aspartic acid at codon 2425 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders 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. |