ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5591A>G (p.Asp1864Gly)

dbSNP: rs786202808
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165818 SCV000216565 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-20 criteria provided, single submitter clinical testing The p.D1864G variant (also known as c.5591A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 5591. The aspartic acid at codon 1864 is replaced by glycine, an amino acid with 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.
Counsyl RCV000412174 SCV000489119 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2016-08-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000820675 SCV000961397 uncertain significance Hereditary breast ovarian cancer syndrome 2020-10-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 1864 of the BRCA2 protein (p.Asp1864Gly). 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 been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 186254). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000165818 SCV003848934 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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