ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.916G>A (p.Asp306Asn)

dbSNP: rs781169306
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001226613 SCV001398934 uncertain significance Hereditary breast ovarian cancer syndrome 2024-03-06 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 306 of the BRCA2 protein (p.Asp306Asn). This variant is present in population databases (rs781169306, gnomAD 0.0009%). 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: 954196). 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 with a negative predictive value of 95%. 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.
Ambry Genetics RCV002375224 SCV002688660 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-02 criteria provided, single submitter clinical testing The p.D306N variant (also known as c.916G>A), located in coding exon 9 of the BRCA2 gene, results from a G to A substitution at nucleotide position 916. The aspartic acid at codon 306 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002375224 SCV003848134 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).

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