ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7339A>G (p.Asn2447Asp)

gnomAD frequency: 0.00001  dbSNP: rs4986859
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165439 SCV000216168 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-25 criteria provided, single submitter clinical testing The p.N2447D variant (also known as c.7339A>G), located in coding exon 13 of the BRCA2 gene, results from an A to G substitution at nucleotide position 7339. The asparagine at codon 2447 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000476866 SCV000549659 uncertain significance Hereditary breast ovarian cancer syndrome 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 2447 of the BRCA2 protein (p.Asn2447Asp). This variant is present in population databases (rs4986859, gnomAD 0.01%). 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: 185933). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284102 SCV001469708 uncertain significance not provided 2020-01-21 criteria provided, single submitter clinical testing
GeneDx RCV001284102 SCV002601536 uncertain significance not provided 2023-07-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as a germline pathogenic or benign variant to our knowledge; Also known as 7567A>G; This variant is associated with the following publications: (PMID: 31191615, 18724707)
Baylor Genetics RCV004567273 SCV005059097 uncertain significance Familial cancer of breast 2024-01-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004782270 SCV005394945 uncertain significance not specified 2024-09-11 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.7339A>G (p.Asn2447Asp) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251078 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.7339A>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 185933). Based on the evidence outlined above, the variant was classified as uncertain significance.
Sharing Clinical Reports Project (SCRP) RCV000238906 SCV000297550 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2011-09-16 no assertion criteria provided clinical testing

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