ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5137del (p.Trp1712_Val1713insTer) (rs80357997)

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Total submissions: 15
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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) RCV000077601 SCV000300209 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000048807 SCV000076820 pathogenic Hereditary breast and ovarian cancer syndrome 2019-11-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val1713*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80357997, ExAC 0.002%). This variant has been observed in families affected with breast cancer, ovarian cancer, and male breast cancer (PMID: 26976419, 7611277, 16683254, 25948282, 27767231), with evidence of segregation with disease (PMID: 7611277). It is also known as 5256delG in the literature. ClinVar contains an entry for this variant (Variation ID: 55411). 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 RCV000131392 SCV000186368 pathogenic Hereditary cancer-predisposing syndrome 2018-09-29 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000235540 SCV000292526 pathogenic not provided 2018-03-29 criteria provided, single submitter clinical testing This deletion of one nucleotide is denoted BRCA1 c.5137delG at the cDNA level and p.Val1713Ter (V1713X) at the protein level. The normal sequence, with the base that is deleted in brackets, is ATGG[delG]TAGT. The deletion creates a nonsense variant, which changes a Valine 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 c.5137delG, previously reported as 5254delG and 5256delG using alternate nomenclature, has been reported in several individuals with Hereditary Breast and Ovarian Cancer syndrome (Struewing 1995, Meindl 2002, Monnerat 2007, Lee 2011, Kluska 2015, Tung 2016). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077601 SCV000296274 pathogenic Breast-ovarian cancer, familial 1 2014-12-15 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077601 SCV000326166 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000048807 SCV000605766 pathogenic Hereditary breast and ovarian cancer syndrome 2017-03-01 criteria provided, single submitter clinical testing The p.Val1713X variant in BRCA1 has been reported in >15 individuals with BRCA1- associated cancers and segregated with disease in >7 affected relatives (Struewi ng 1995, Monnerat 2007, Breast Cancer Information Core (BIC) database). It was a lso identified in 1/66198 European chromosomes by the Exome Aggregation Consorti um (ExAC, http://exac.broadinstitute.org; dbSNP rs80357997); however, this frequ ency is low enough to be consistent with the frequency of hereditary breast and ovarian cancer (HBOC) in the general population. This variant is a deletion of a single nucleotide, which generates a premature termination codon at position 17 13, which is predicted to lead to a truncated or absent protein. Heterozygous lo ss of function of the BRCA1 gene is an established disease mechanism in HBOC. Fu rthermore, this variant was classified as Pathogenic on September 8, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000300209.2). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner.
Counsyl RCV000077601 SCV000677658 pathogenic Breast-ovarian cancer, familial 1 2015-09-29 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000131392 SCV000679697 pathogenic Hereditary cancer-predisposing syndrome 2017-07-12 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077601 SCV000744597 pathogenic Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Color RCV000131392 SCV000911169 pathogenic Hereditary cancer-predisposing syndrome 2017-10-09 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077601 SCV000109404 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077601 SCV000145323 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048807 SCV000587469 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077601 SCV000733597 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing

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