ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.514del (p.Gln172fs) (rs80357872)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130785 SCV000185678 pathogenic Hereditary cancer-predisposing syndrome 2018-04-12 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) RCV000083216 SCV000145606 pathogenic Breast-ovarian cancer, familial 1 1999-12-30 no assertion criteria provided clinical testing
Color RCV000130785 SCV000910961 pathogenic Hereditary cancer-predisposing syndrome 2017-03-20 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083216 SCV000326170 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048817 SCV000591275 pathogenic Hereditary breast and ovarian cancer syndrome 2013-09-16 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000083216 SCV000282337 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 RCV000735470 SCV000863607 pathogenic Breast and/or ovarian cancer 2013-12-03 no assertion criteria provided clinical testing
GeneDx RCV000212158 SCV000210002 pathogenic not provided 2018-12-17 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.514delC at the cDNA level and p.Gln172AsnfsX62 (Q172NfsX62) at the protein level. The normal sequence, with the base that is deleted in brackets, is GATA[delC]AACC. The deletion causes a frameshift, which changes a Glutamine to an Asparagine at codon 172 and creates a premature stop codon at position 62 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.514delC, previously reported as 633delC using alternate nomenclature, has been observed in several Hereditary Breast and Ovarian Cancer families (van Orsouw 1999, Tai 2007, Ghiorzo 2012, Finch 2015) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000048817 SCV000916783 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-16 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.514delC (p.Gln172AsnfsX62) 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. The variant allele was found at a frequency of 8.2e-06 in 121410 control chromosomes (ExAC). The variant, c.514delC, has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Azzollini_2016, Wong-Brown_2015, Tai_2007). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six 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.
Invitae RCV000048817 SCV000076830 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln172Asnfs*62) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80357872, ExAC 0.001%). This variant has been observed in individuals with breast, ovarian and pancreatic cancer (PMID: 10528853, 17591842, 21989927, 26219728, 25682074). This variant is also known as 633delC in the literature. ClinVar contains an entry for this variant (Variation ID: 55421). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212158 SCV000296357 pathogenic not provided 2015-07-03 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048817 SCV000587058 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000083216 SCV000115290 pathogenic Breast-ovarian cancer, familial 1 2009-11-23 no assertion criteria provided clinical testing

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