ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5705A>G (p.Asp1902Gly)

dbSNP: rs2072536350
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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 RCV001245899 SCV001419223 uncertain significance Hereditary breast ovarian cancer syndrome 2019-11-02 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 1902 of the BRCA2 protein (p.Asp1902Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158617 SCV003849028 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).
Ambry Genetics RCV003158617 SCV005102177 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-20 criteria provided, single submitter clinical testing The p.D1902G variant (also known as c.5705A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 5705. The aspartic acid at codon 1902 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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