ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3989A>G (p.Asn1330Ser)

dbSNP: rs1057520792
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000442000 SCV000517459 likely benign not specified 2015-06-11 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health RCV000775925 SCV000910414 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001038220 SCV001201683 uncertain significance Hereditary breast ovarian cancer syndrome 2023-04-14 criteria provided, single submitter clinical testing 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: 379934). 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 serine, which is neutral and polar, at codon 1330 of the BRCA2 protein (p.Asn1330Ser).
Ambry Genetics RCV000775925 SCV002622465 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-09 criteria provided, single submitter clinical testing The p.N1330S variant (also known as c.3989A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 3989. The asparagine at codon 1330 is replaced by serine, an amino acid with highly similar properties. This alteration was observed with an allele frequency of 0.00009 in 11,241 female controls of Japanese ancestry and was not observed in 7,051 unselected female breast cancer cases. In addition, it was not observed in unselected male breast cancer patients and was observed with an allele frequency of 0.0002 in 12,490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000775925 SCV003848586 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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