ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.799G>T (p.Gly267Ter) (rs786202796)

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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 RCV000165786 SCV000216531 pathogenic Hereditary cancer-predisposing syndrome 2016-02-10 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)
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000241277 SCV000300363 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000220294 SCV000278835 pathogenic not provided 2015-12-04 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.799G>T at the cDNA level and p.Gly267Ter (G267X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 c.1027G>T. The substitution creates a nonsense variant, which changes a Glycine to a premature stop codon (GGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000781052 SCV000918837 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-02-22 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.799G>T (p.Gly267X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.846_847delCA/p.Ile283fsX11). The variant was absent in 239416 control chromosomes. To our knowledge, no occurrence of c.799G>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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