ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.708T>C (p.His236=) (rs185506536)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495426 SCV000579132 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 RCV000163130 SCV000213643 likely benign Hereditary cancer-predisposing syndrome 2014-10-08 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001082184 SCV000261849 benign Hereditary breast and ovarian cancer syndrome 2020-12-08 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735601 SCV000324850 likely benign Breast and/or ovarian cancer 2016-02-19 criteria provided, single submitter clinical testing
GeneDx RCV000436215 SCV000515798 benign not specified 2015-04-15 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.
Genetic Services Laboratory, University of Chicago RCV000436215 SCV000593699 likely benign not specified 2016-02-25 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163130 SCV000683850 likely benign Hereditary cancer-predisposing syndrome 2016-07-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000436215 SCV000695037 likely benign not specified 2019-04-25 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.708T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 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 2.5e-05 in 275394 control chromosomes (gnomAD and Momozawa 2018). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.708T>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Seven other submitters including one expert panel have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign (1x) / likely benign (6x). Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587408 SCV000887900 likely benign not provided 2019-11-11 criteria provided, single submitter clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735601 SCV000863739 uncertain significance Breast and/or ovarian cancer 2014-05-26 no assertion criteria provided clinical testing

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