ClinVar Miner

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

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045597 SCV000073610 likely benign Hereditary breast and ovarian cancer syndrome 2017-10-19 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 Lines of evidence used in support of classification: 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 RCV000587037 SCV000695171 uncertain significance not provided 2017-03-24 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.8668C>A (p.Leu2890Ile) variant involves the alteration of a not conserved nucleotide. 3/5 in silico tools predict a damaging outcome for this variant. This variant was found in 3/120708 control chromosomes at a frequency of 0.0000249, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been reported in the literature, without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS.
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 2018-06-06 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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