ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2071del (p.Arg691fs) (rs80357688)

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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131404 SCV000186380 pathogenic Hereditary cancer-predisposing syndrome 2018-03-15 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)
Bioinformatics dept.,Datar Cancer Genetics Limited, India RCV000031025 SCV000583989 pathogenic Breast-ovarian cancer, familial 1 2017-07-07 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031025 SCV000144286 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131404 SCV000683010 pathogenic Hereditary cancer-predisposing syndrome 2015-04-01 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031025 SCV000325224 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031025 SCV000487819 pathogenic Breast-ovarian cancer, familial 1 2015-11-18 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000167861 SCV000591365 pathogenic Hereditary breast and ovarian cancer syndrome 2014-03-27 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000167861 SCV000588038 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000047699 SCV000708438 pathogenic not provided 2017-05-15 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031025 SCV000282272 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 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 RCV000735450 SCV000863587 pathogenic Breast and/or ovarian cancer 2009-12-01 no assertion criteria provided clinical testing
GeneDx RCV000047699 SCV000210019 pathogenic not provided 2018-06-13 criteria provided, single submitter clinical testing This deletion of a single nucleotide is denoted BRCA1 c.2071delA at the cDNA level and p.Arg691AspfsX10 (R691DfsX10) at the protein level. This deletion is also known as BRCA1 2190delA using alternate nomenclature. The normal sequence, with the base that is deleted in brackets, is TAAA[delA]GACA. The deletion causes a frameshift, which changes an Arginine to an Aspartic Acid at codon 691, and creates a premature stop codon at position 10 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 c.2071delA has been reported in several individuals with ovarian cancer or hereditary breast/ovarian cancer (Gayther 1999, Risch 2006, Sharif 2007, Zhang 2011, Song 2014, Pal 2015). We consider this variant to be pathogenic.
Genetic Services Laboratory, University of Chicago RCV000031025 SCV000593692 pathogenic Breast-ovarian cancer, familial 1 2017-05-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000167861 SCV000698915 pathogenic Hereditary breast and ovarian cancer syndrome 2017-05-11 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2071delA (p.Arg691Aspfs) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2138C>G, p.Ser713X; c.2157dupA, p.Glu720fs). One in silico tool predicts a damaging outcome for this variant. The variant of interest is absent in a large, broad control population, ExAC in 121338 control chromosomes. This variant was reported in multiple patients with HBOC (Judkins_2005, Trujillano_2014, Peto_1999, Frank_1998, Risch_2001, Zhang_2011). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000167861 SCV000075712 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg691Aspfs*10) 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 reported in the literature in multiple affected individuals with family history of breast and/or ovarian cancer (PMID: 9482581, 21324516, 24504028, 9667259, 10486320). This variant is also known as 2190delA in the literature. ClinVar contains an entry for this variant (Variation ID: 37444). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000047699 SCV000778764 pathogenic not provided 2017-05-16 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000167861 SCV000587182 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031025 SCV000053618 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing

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