ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.466_467CT[2] (p.Leu156_Ser157insTer) (rs80357887)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031189 SCV000282333 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000203622 SCV000076650 pathogenic Hereditary breast and ovarian cancer syndrome 2019-12-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser157*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals and families affected with breast and ovarian cancer (PMID: 11149413, 22970155, 23683081, 24916970). This variant is also known as 589delCT. ClinVar contains an entry for this variant (Variation ID: 37608). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131836 SCV000186891 pathogenic Hereditary cancer-predisposing syndrome 2019-04-22 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)
GeneDx RCV000048637 SCV000210001 pathogenic not provided 2018-12-12 criteria provided, single submitter clinical testing This deletion of 2 nucleotides is denoted BRCA1 c.470_471delCT at the cDNA level and p.Ser157Ter (S157X) at the protein level. The normal sequence, with the bases that are deleted in braces, is CTCT[CT]AACC. The deletion creates a nonsense variant, which changes a Serine to a premature stop codon. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 470_471delCT, previously reported as 589delCT, has been published in association with early-onset and/or familial breast and ovarian cancer and has been reported as a recurrent variant in Asian, Spanish, and Portuguese populations (Tang 1999, de la Hoya 2001, Kwong 2012, Blay 2013, Peixoto 2015). We therefore consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031189 SCV000326035 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Color RCV000131836 SCV000688515 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Mendelics RCV000203622 SCV000839303 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000048637 SCV000888925 pathogenic not provided 2018-07-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000203622 SCV001432093 pathogenic Hereditary breast and ovarian cancer syndrome 2020-08-10 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.470_471delCT (p.Ser157X) 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. The variant was absent in 251450 control chromosomes. c.470_471delCT has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (delaHoya_2002, Judkins_2005, Kwong_2012, Peixoto_2014). These data indicate that the variant is very likely to be associated with disease. Eight 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.
Sharing Clinical Reports Project (SCRP) RCV000031189 SCV000053789 pathogenic Breast-ovarian cancer, familial 1 2010-08-27 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031189 SCV000145594 not provided Breast-ovarian cancer, familial 1 no assertion provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000203622 SCV000587056 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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