ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6413T>A (p.Val2138Asp) (rs80358877)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223184 SCV000278773 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000767077 SCV000565988 uncertain significance not provided 2016-10-31 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6413T>A at the cDNA level, p.Val2138Asp (V2138D) at the protein level, and results in the change of a Valine to an Aspartic Acid (GTT>GAT). Using alternate nomenclature, this variant would be defined as BRCA2 6641T>A. BRCA2 Val2138Asp was observed in at least one individual with a personal history of a Lynch syndrome-assoicated cancer and/or colon polyps (Yurgelun 2015). This variant was also identified in 1/118 healthy Hispanic individuals undergoing whole genome sequencing (Bodian 2014). Of note, the participants in this study were younger than 50 years old thus the unaffected status of this individual may not be significant. BRCA2 Val2138Asp 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 Valine and Aspartic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Val2138Asp occurs at a position that is not conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA2 Val2138Asp is pathogenic or benign. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000120349 SCV000600700 uncertain significance not specified 2017-04-01 criteria provided, single submitter clinical testing
Color RCV000223184 SCV000911868 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-25 criteria provided, single submitter clinical testing
ITMI RCV000120349 SCV000084501 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA2) RCV000113585 SCV000146847 uncertain significance Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000120349 SCV000587844 uncertain significance not specified 2014-01-31 no assertion criteria provided research

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