ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5161C>T (p.Gln1721Ter) (rs878854957)

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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 RCV000571650 SCV000661104 pathogenic Hereditary cancer-predisposing syndrome 2016-12-20 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 RCV000256774 SCV000326189 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000256774 SCV000323841 pathogenic Breast-ovarian cancer, familial 1 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Integrated Genetics/Laboratory Corporation of America RCV000781017 SCV000918770 pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-13 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5161C>T (p.Gln1721X) 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.5177_5180delGAAA, p.Arg1726fsX3; c.5182delA, p.Met1728fsX2; c.5239C>T, p.Gln1747X). The variant was absent in 245790 control chromosomes (gnomAD). The variant, c.5161C>T, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Muendlein_2015, Nakamura_2013, Minucci_2015). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has 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 pathogenic.

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