ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2475del (p.Asp825fs) (rs80357970)

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Total submissions: 16
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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) RCV000031053 SCV000282281 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 RCV000047850 SCV000075863 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp825Glufs*21) 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 individuals with breast cancer, ovarian cancer, and prostate cancer (PMID: 8595428, 22160602, 22516946, 24504028, 20104584, 24307375). This variant is a well-known disease causing variant in the Scandinavian population (PMID: 23199084, 18465347, 23704984). In the literature, this variant is also known as 2594delC. ClinVar contains an entry for this variant (Variation ID: 37472). 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 RCV000131352 SCV000186327 pathogenic Hereditary cancer-predisposing syndrome 2017-10-24 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)
Michigan Medical Genetics Laboratories,University of Michigan RCV000031053 SCV000195906 pathogenic Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
GeneDx RCV000236906 SCV000292513 pathogenic not provided 2018-06-07 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.2475delC at the cDNA level and p.Asp825GlufsX21 (D825EfsX21) at the protein level. The normal sequence, with the base that is deleted in brackets, is ATGA[delC]ACAG. The deletion causes a frameshift, which changes an Aspartic Acid to a Glutamic Acid at codon 825, and creates a premature stop codon at position 21 of the new reading frame. BRCA1 c.2475delC is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also known as BRCA1 2594delC using alternate nomenclature, has been published in association with breast, ovarian, and prostate cancer, and is reported as a recurrent variant in Scandinavian populations (Plummer 1995, Janavicius 2010, Leongamornlert 2012, Schneegans 2012, Pennington 2013, Cunningham 2014). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236906 SCV000296289 pathogenic not provided 2019-02-15 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031053 SCV000325365 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000031053 SCV000564368 pathogenic Breast-ovarian cancer, familial 1 2015-07-21 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000047850 SCV000586884 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-18 criteria provided, single submitter clinical testing
Counsyl RCV000031053 SCV000677643 pathogenic Breast-ovarian cancer, familial 1 2015-04-01 criteria provided, single submitter clinical testing
Color RCV000131352 SCV000683038 pathogenic Hereditary cancer-predisposing syndrome 2016-08-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000047850 SCV000698959 pathogenic Hereditary breast and ovarian cancer syndrome 2016-06-08 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2475delC (p.Asp825Glufs) 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.2515delC, c.2679_2682delGAAA, c.2681_2682delAA). One in silico tool predicts a damaging outcome for this variant and the variant is absent in 121366 control chromosomes. The variant has been reported in numerous affected families and individuals in the literature, and has been described as a common mutation in individuals of Scandinavian ancestry. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031053 SCV000053647 pathogenic Breast-ovarian cancer, familial 1 2013-02-04 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031053 SCV000144450 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 RCV000047850 SCV000587221 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785403 SCV000923975 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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