ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.843_846del (p.Ser282fs) (rs80357919)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131872 SCV000186927 pathogenic Hereditary cancer-predisposing syndrome 2017-10-10 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)
Breast Cancer Information Core (BIC) (BRCA1) RCV000019253 SCV000145702 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131872 SCV000683371 pathogenic Hereditary cancer-predisposing syndrome 2016-01-04 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000019253 SCV000326442 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000019253 SCV000564365 pathogenic Breast-ovarian cancer, familial 1 2015-06-28 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000049168 SCV000591305 pathogenic Hereditary breast and ovarian cancer syndrome 2012-02-03 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000019253 SCV000733664 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000019253 SCV000299490 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735511 SCV000863649 pathogenic Breast and/or ovarian cancer 2000-08-01 no assertion criteria provided clinical testing
GeneDx RCV000412670 SCV000210005 pathogenic not provided 2016-12-08 criteria provided, single submitter clinical testing This deletion of four nucleotides in BRCA1 is denoted c.843_846delCTCA at the cDNA level and p.Ser282TyrfsX15 (S282YfsX15) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CCAG[delCTCA]TTAC. The deletion causes a frameshift, which changes a Serine to a Tyrosine at codon 282, and creates a premature stop codon at position 15 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 843_846delCTCA, previously reported as 962del4 using alternate nomenclature, has been reported in numerous individuals with personal and/or family histories of breast and/or ovarian cancer (Wagner 1998, Janezic 1999, Risch 2001, Stegel 2011, Zhang 2011, Pern 2012, Song 2014, Muendlein 2015). We consider this variant to be pathogenic.
GeneKor MSA RCV000412670 SCV000296764 pathogenic not provided 2018-08-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000049168 SCV000699318 pathogenic Hereditary breast and ovarian cancer syndrome 2016-07-01 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.843_846delCTCA (p.Ser282Tyrfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant is not located in any known functional domain of the BRCA1 protein, but if a truncated protein is made, it is predicted to eliminate the serine-rich domain and the BRCT domain. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.844_850deldupTCATAC/p.Gln284fs). One in silico tool predicts a damaging outcome for this variant. This variant was absent in 124266 control chromosomes and has been reported in many affected patients. Additionally, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant was classified as pathogenic.
Invitae RCV000049168 SCV000077181 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-17 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotides from exon 10 of the BRCA1 mRNA (c.843_846delCTCA), causing a frameshift at codon 282. This creates a premature translational stop signal (p.Ser282Tyrfs*15) 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 the literature in individuals with breast and/or ovarian cancer (PMID: 9663595, 10196379, 21324156, 23110154, 17319787, 21203900). This variant is also known as 962del4 in the literature. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019253 SCV000039541 pathogenic Breast-ovarian cancer, familial 1 1999-05-01 no assertion criteria provided literature only
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000412670 SCV000600442 pathogenic not provided 2017-03-25 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000049168 SCV000587080 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000019253 SCV000109435 pathogenic Breast-ovarian cancer, familial 1 2013-05-28 no assertion criteria provided clinical testing

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