ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2157dup (p.Glu720fs) (rs80357715)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000111778 SCV000299708 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Vantari Genetics RCV000210761 SCV000267010 pathogenic Hereditary cancer-predisposing syndrome 2015-11-27 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111778 SCV000325271 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000047735 SCV000698925 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-16 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2157dupA (p.Glu720Argfs) 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. A truncated protein product, p.Glu720Argfs). One in silico tool predicts a damaging outcome for this variant. This variant was absent in 121246 control chromosomes, but has been cited in multiple cases of familial breast cancer in the literature. Furthermore, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
GeneDx RCV000657212 SCV000778938 pathogenic not provided 2016-11-28 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA1 is denoted c.2157dupA at the cDNA level and p.Glu720ArgfsX6 (E720RfsX6) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 2276dupA or 2274insA. The normal sequence, with the base that is duplicated in brackets, is TTAA[dupA]GAAT. The duplication causes a frameshift which changes a Glutamic Acid to an Arginine at codon 720, and creates a premature stop codon at position 6 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.2157dupA has been reported in association with hereditary breast and ovarian cancer (Machackova 2008, Trujillano 2015). We consider this variant to be pathogenic.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769720 SCV000901140 pathogenic Breast and/or ovarian cancer 2017-08-30 criteria provided, single submitter clinical testing
Invitae RCV000047735 SCV000075748 pathogenic Hereditary breast and ovarian cancer syndrome 2014-11-06 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000111778 SCV000144313 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000047735 SCV000587191 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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.