ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2389_2390del (p.Glu797fs) (rs80357695)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162855 SCV000213342 pathogenic Hereditary cancer-predisposing syndrome 2018-03-07 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)
Breast Cancer Information Core (BIC) (BRCA1) RCV000083182 SCV000144401 pathogenic Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083182 SCV000325339 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) RCV000083182 SCV000299757 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Integrated Genetics/Laboratory Corporation of America RCV000047820 SCV000918700 pathogenic Hereditary breast and ovarian cancer syndrome 2018-04-30 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2389_2390delGA (p.Glu797ThrfsX3) 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.2411_2412delAG, p.Gln804fsX5; c.2433delC, p.Lys812fsX3; c.2457delC, p.Asp821fsX25). The variant was absent in 121326 control chromosomes (ExAC). The variant, c.2389_2390delGA, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer, including in one family where it segregated with disease (Alsop_2012, Kawahara_2004, Kashima_2000, Yoshikawa_1999). 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. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000047820 SCV000075833 pathogenic Hereditary breast and ovarian cancer syndrome 2017-06-16 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 10 of the BRCA1 mRNA (c.2389_2390delGA), causing a frameshift at codon 797. This creates a premature translational stop signal (p.Glu797Thrfs*3) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic. This particular variant has been reported in individuals affected with breast and ovarian cancer (PMID: 10634513, 25070656). This variant is also known as 2508delGA in the literature. For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507145 SCV000600286 pathogenic not provided 2016-09-30 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083182 SCV000115256 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing

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