ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4111C>T (p.Gln1371Ter) (rs80358659)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
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) RCV000077320 SCV000300708 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000044353 SCV000072366 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1371*) in the BRCA2 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 observed in individuals affected with breast cancer (PMID: 25371446). ClinVar contains an entry for this variant (Variation ID: 51599). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131073 SCV000186003 pathogenic Hereditary cancer-predisposing syndrome 2017-11-21 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)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000478066 SCV000296507 pathogenic not provided 2016-05-24 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077320 SCV000326972 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000478066 SCV000567705 pathogenic not provided 2018-11-14 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.-48G>T, and describes a nucleotide substitution 48 base pairs upstream of the MSH2 ATG translational start site in the 5' untranslated region (UTR). The surrounding sequence, with the base that is substituted in braces, is GTGG[G/T]TGTG. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 c.-48G>T does not appear to affect the start codon or the Kozak translational consensus sequence and the nucleotide which is altered is not conserved. At this time, we consider MSH2 c.-48G>T to be a variant of uncertain significance.
Color RCV000131073 SCV000688849 pathogenic Hereditary cancer-predisposing syndrome 2017-09-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044353 SCV000694744 pathogenic Hereditary breast and ovarian cancer syndrome 2016-05-09 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.4111C>T (p.Gln1371X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Mutation taster predicts a damaging outcome for this variant. The variant is absent in 120892 control chromosomes while it was reported in at least five HBOC spectrum patients indicating pathogenicity. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Ser1630X, p.Tyr1569X) further supporting a deleterious impact of this variant. In addition, multiple clinical diagnostic laboratories have classified this variant as Pathogenic. Taken together, this variant is classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077320 SCV000109117 pathogenic Breast-ovarian cancer, familial 2 2012-01-24 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077320 SCV000146376 pathogenic Breast-ovarian cancer, familial 2 1998-02-06 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044353 SCV000587699 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.