ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3100dup (p.Ile1034fs)

dbSNP: rs886040460
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
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) RCV000256799 SCV000324133 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000256799 SCV000326812 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000496292 SCV004848416 likely pathogenic Hereditary breast ovarian cancer syndrome 2020-06-19 criteria provided, single submitter clinical testing The p.Ile1034AsnfsX2 variant in BRCA2 has not been reported in the literature in individuals with hereditary breast and/or ovarian cancer (HBOC) and was absent from large population studies. However, this variant was classified as pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000324133.1). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1034 and leads to a premature termination codon 2 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the BRCA2 gene is an established disease mechanism in autosomal dominant HBOC. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant hereditary breast and ovarian cancer. ACMG/AMP codes applied: PVS1, PM2.
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto RCV000496292 SCV000587655 pathogenic Hereditary breast 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.