ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1838T>G (p.Leu613Arg) (rs587780646)

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
Invitae RCV000122900 SCV000166158 likely benign Hereditary breast and ovarian cancer syndrome 2020-01-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129425 SCV000184195 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-24 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000221850 SCV000278839 likely benign not specified 2017-07-05 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985248 SCV000296608 uncertain significance not provided 2019-04-19 criteria provided, single submitter clinical testing
Counsyl RCV000238635 SCV000489192 uncertain significance Breast-ovarian cancer, familial 2 2016-08-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000221850 SCV000694575 uncertain significance not specified 2019-06-17 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.1838T>G (p.Leu613Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.4e-05 in 241822 control chromosomes, predominantly at a frequency of 0.00051 within the Latino subpopulation in the gnomAD database. This frequency is not higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (7.4e-05 vs 0.00075), allowing no conclusion about variant significance. This variant has been reported in one Latino (Mexican) patient with breast cancer who had positive family history of breast (a sister and a paternal cousin) and other cancers (leukemia and prostate cancer) (Ruiz-Flores_2002). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments, two classified as likely benign while four classified as VUS. Based on the evidence outlined above, the variant was classified as uncertain significance.
Color RCV000129425 SCV000903069 likely benign Hereditary cancer-predisposing syndrome 2017-01-03 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000238635 SCV000297506 likely benign Breast-ovarian cancer, familial 2 2013-09-11 no assertion criteria provided clinical testing

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.