ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3436G>T (p.Glu1146Ter) (rs1237049560)

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
Ambry Genetics RCV000509826 SCV000608236 pathogenic Hereditary cancer-predisposing syndrome 2015-11-02 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)
Color RCV000509826 SCV000912368 pathogenic Hereditary cancer-predisposing syndrome 2017-11-30 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000661493 SCV000783778 pathogenic Breast-ovarian cancer, familial 2 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Integrated Genetics/Laboratory Corporation of America RCV000780006 SCV000916996 likely pathogenic Hereditary breast and ovarian cancer syndrome 2017-12-15 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3436G>T (p.Glu1146X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., p.Phe1182fsX1 and p.Lys1191fsX6). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/245794 control chromosomes at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). One clinical diagnostic laboratory classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.

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.