ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4494T>A (p.Gly1498=) (rs373160367)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
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) RCV000494989 SCV000578744 likely benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics RCV000163657 SCV000214227 likely benign Hereditary cancer-predisposing syndrome 2014-09-18 criteria provided, single submitter clinical testing
Invitae RCV000226722 SCV000283239 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000426463 SCV000517852 likely benign not specified 2018-02-27 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000494989 SCV000743298 likely benign Breast-ovarian cancer, familial 2 2016-11-08 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000494989 SCV000744456 likely benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Color RCV000163657 SCV000911199 likely benign Hereditary cancer-predisposing syndrome 2017-03-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000426463 SCV000918832 uncertain significance not specified 2018-05-22 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.4494T>A alters a non-conserved nucleotide resulting in a synonymous change. 3/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.4e-05 in 245234 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (2.4e-05 vs 0.00075), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.4494T>A in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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.