ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8668C>A (p.Leu2890Ile) (rs80359127)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001082637 SCV000073610 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131717 SCV000186756 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-26 criteria provided, single submitter clinical testing Other data supporting benign classification;Insufficient or Conflicting Evidence
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000587037 SCV000227749 uncertain significance not provided 2014-11-21 criteria provided, single submitter clinical testing
GeneDx RCV000587037 SCV000278882 uncertain significance not provided 2018-07-11 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8668C>A at the cDNA level, p.Leu2890Ile (L2890I) at the protein level, and results in the change of a Leucine to an Isoleucine (CTA>ATA). Using alternate nomenclature, this variant would be defined as BRCA2 8896C>A. BRCA2 Leu2890Ile has been reported in at least one individual with prostate cancer (Kote-Jarai 2011). BRCA2 Leu2890Ile was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in 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 Leu2890Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000077447 SCV000489154 uncertain significance Breast-ovarian cancer, familial 2 2016-08-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001175344 SCV000695171 uncertain significance not specified 2019-12-16 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8668C>A (p.Leu2890Ile) results in a 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 1.6e-05 in 251326 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.8668C>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Karchin_2008) and other cancer phenotypes (Kote-Jarai_2011, Deihimi_2017). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrence with another pathogenic variant has been reported (BRCA1 c.3340G>T, p.Glu1114*; internal database), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar (evaluation after 2014) and cited the variant as uncertain significance (n=4) and likely benign (n=2). Based on the evidence outlined above, the variant was classified as uncertain significance.
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077447 SCV000744545 likely benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Color RCV000131717 SCV000911249 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-23 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587037 SCV001133942 uncertain significance not provided 2019-05-01 criteria provided, single submitter clinical testing
Mendelics RCV000077447 SCV001139224 uncertain significance Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077447 SCV000109245 likely benign Breast-ovarian cancer, familial 2 2012-05-07 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077447 SCV000147435 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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