ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3485del (p.Asp1162fs) (rs80357509)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 16
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220121 SCV000273760 pathogenic Hereditary cancer-predisposing syndrome 2017-07-25 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)
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000408844 SCV000484951 pathogenic Familial cancer of breast no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031112 SCV000144775 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000220121 SCV000688438 pathogenic Hereditary cancer-predisposing syndrome 2015-01-20 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031112 SCV000325669 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Curoverse RCV000048213 SCV000245336 pathogenic Hereditary breast and ovarian cancer syndrome 2015-08-01 no assertion criteria provided research Frameshifts in BRCA1 are considered pathogenic, and this is a BRCA1 Asp1162Val frameshift variant in exon 10
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031112 SCV000744634 pathogenic Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000031112 SCV000733627 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031112 SCV000299952 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000159918 SCV000210041 pathogenic not provided 2018-12-05 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA1 is denoted c.3485delA at the cDNA level and p.Asp1162ValfsX48 (D1162VfsX48) at the protein level. The normal sequence, with the base that is deleted in brackets, is GAAG[delA]TACT. The deletion causes a frameshift, which changes an Aspartic Acid to a Valine at codon 1162, and creates a premature stop codon at position 48 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.3485delA, also reported as BRCA1 3604delA, has been observed in several hereditary breast and ovarian cancer families and has been described as a pathogenic founder variant in Finnish and Dutch populations (Peelen 1997, Vehmanen 1997, Syrjakoski 2000, Janavicius 2010, Brohet 2014). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000048213 SCV000699038 pathogenic Hereditary breast and ovarian cancer syndrome 2017-07-06 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3485delA (p.Asp1162Valfs) 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.3582_3589delCCATACAC/ p.His1195fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121314 control chromosomes. This variant has been reported in many affected individuals and multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000048213 SCV000076226 pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-25 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 10 of the BRCA1 mRNA (c.3485delA), causing a frameshift at codon 1162. This creates a premature translational stop signal (p.Asp1162Valfs*48) 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 affected with breast and/or ovarian cancer (PMID: 9150151, 24010542, 16683254, 26681312, 25452441). This variant is also known as 3604delA, c.3625delA, and 3741delA in the literature. For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000048213 SCV000605763 pathogenic Hereditary breast and ovarian cancer syndrome 2017-01-27 criteria provided, single submitter clinical testing The p.Asp1162fs variant in BRCA1 has been reported in >30 individuals with BRCA1 -associated cancers (Peelen 1997, Breast Cancer Information Core (BIC) database) and was absent from large population studies. This variant is predicted to caus e a frameshift, which alters the protein?s amino acid sequence beginning at posi tion 1162 and leads to a premature termination codon 48 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Hete rozygous loss of function of function of the BRCA1 gene is an established diseas e mechanism in hereditary breast and ovarian cancer (HBOC). In addition, this va riant was classified as Pathogenic on September 8, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000299952.2). In summary, the p.Asp1162fs varian t meets criteria to be classified as pathogenic for HBOC in an autosomal dominan t manner.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159918 SCV000600335 pathogenic not provided 2016-09-11 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048213 SCV000587316 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031112 SCV000053709 pathogenic Breast-ovarian cancer, familial 1 2014-04-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.