ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8807T>C (p.Leu2936Ser) (rs398122714)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132403 SCV000187495 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-22 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000587247 SCV000210485 uncertain significance not provided 2019-01-03 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8807T>C at the cDNA level, p.Leu2936Ser (L2936S) at the protein level, and results in the change of a Leucine to a Serine (TTG>TCG). Using alternate nomenclature, this variant would be defined as BRCA2 9035T>C. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BRCA2 Leu2936Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the DNA binding domain (Yang 2002). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Leu2936Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000587247 SCV000227873 uncertain significance not provided 2014-08-11 criteria provided, single submitter clinical testing
Invitae RCV000198146 SCV000254221 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-08 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000198146 SCV000267848 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-04-25 criteria provided, single submitter clinical testing
Counsyl RCV000077643 SCV000488314 uncertain significance Breast-ovarian cancer, familial 2 2016-02-24 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160158 SCV000600826 uncertain significance not specified 2016-12-16 criteria provided, single submitter clinical testing
Color RCV000132403 SCV000683999 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000160158 SCV000695183 uncertain significance not specified 2019-10-11 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8807T>C (p.Leu2936Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 250694 control chromosomes. 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.8807T>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Seven 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 uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587247 SCV000889168 uncertain significance not provided 2018-02-18 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077643 SCV000109446 likely benign Breast-ovarian cancer, familial 2 2012-09-19 no assertion criteria provided clinical testing

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