ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5784A>C (p.Glu1928Asp) (rs431825335)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000580238 SCV000683734 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-13 criteria provided, single submitter clinical testing
GeneDx RCV000523964 SCV000617250 uncertain significance not provided 2017-04-10 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.5784A>C at the cDNA level, p.Glu1928Asp (E1928D) at the protein level, and results in the change of a Glutamic Acid to an Aspartic Acid (GAA>GAC). This variant, also known as BRCA2 6012A>C using alternate nomenclature, has been reported in at least one individual with breast cancer (Park 2016). BRCA2 Glu1928Asp was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Glutamic Acid and Aspartic Acid share similar properties, this is considered a conservative amino acid substitution. BRCA2 Glu1928Asp occurs at a position that is not conserved and is located in the RAD51 binding domain (Roy 2012). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Glu1928Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000122919 SCV000166177 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 1928 of the BRCA2 protein (p.Glu1928Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer (PMID: 27124784). ClinVar contains an entry for this variant (Variation ID: 96829). 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, this variant has uncertain impact on BRCA2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000082950 SCV000115024 uncertain significance Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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