ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3775A>C (p.Ser1259Arg) (rs587782071)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130561 SCV000185432 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
GeneDx RCV000213541 SCV000279566 uncertain significance not provided 2015-11-11 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3775A>C at the cDNA level, p.Ser1259Arg (S1259R) at the protein level, and results in the change of a Serine to an Arginine (AGT>CGT). Using alternate nomenclature, this variant would be defined as BRCA2 4003A>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Ser1259Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Serine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Ser1259Arg occurs at a position that is not conserved and is located in the BRC repeats (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 Ser1259Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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