ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9381G>A (p.Trp3127Ter) (rs876661242)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000568965 SCV000661241 pathogenic Hereditary cancer-predisposing syndrome 2017-02-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000256847 SCV000328121 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000256847 SCV000324769 pathogenic Breast-ovarian cancer, familial 2 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000219823 SCV000279877 pathogenic not provided 2016-02-08 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9381G>A at the cDNA level and p.Trp3127Ter (W3127X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also reported as BRCA2 9609G>A, has been reported in an individual with a personal or family history of breast and/or ovarian cancer (Ricci 2014) and is considered pathogenic.
Invitae RCV000229281 SCV000283365 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 3127 (p.Trp3127*). It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This particular variant has been reported in the literature in an individual with suspected hereditary breast and ovarian cancer syndrome (PMID: 24065114). For these reasons, this variant has been classified as Pathogenic.

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