ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9116C>T (p.Pro3039Leu) (rs80359167)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131718 SCV000186757 likely benign Hereditary cancer-predisposing syndrome 2017-09-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Intact protein function observed in appropriate functional assay(s),Other data supporting benign classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000083154 SCV000147542 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000131718 SCV000910794 benign Hereditary cancer-predisposing syndrome 2016-07-21 criteria provided, single submitter clinical testing
Department of Medical Genetics,University Hospital of North Norway RCV000083154 SCV000301455 uncertain significance Breast-ovarian cancer, familial 2 2016-05-01 no assertion criteria provided clinical testing
GeneDx RCV000254649 SCV000210680 likely benign not specified 2018-02-05 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.
Genetic Services Laboratory, University of Chicago RCV000254649 SCV000593758 likely benign not specified 2016-04-19 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000254649 SCV000917011 likely benign not specified 2017-12-11 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9116C>T (p.Pro3039Leu) variant involves the alteration of a non-conserved nucleotide located two nucleotides upstream from the exon 23-intron 23 junction. 4/5 in silico tools predict a damaging outcome for this variant. 3/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts loss/weakening effects on binding sites for splicing enhancers. To this date, at least 4 independent research groups showed that this variant has no effect on splicing (Colombo_2013, Caux-Moncoutier_2009, Houdayer_2012, Menendez_2012). This variant was found in 21/243206 control chromosomes (gnomAD) at a frequency of 0.0000863, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been reported by UMD in one individual who also carried the deleterious variant BRCA1 c.670+1G>T, a strong evidence for a benign outcome. Individuals with HBOC have been reported in the literature without information about co-segregation and co-occurrence (Park_2017, Azzollini_2016, Rodriguez-Balada_2016, Coulet_2010). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Considering all available lines of evidence, including the pathogenic co-occurrence and that multiple in-vitro studies show no splicing effect and at-least one computational study (Karchin_2008) predicting a neutral outcome, this variant is classified as likely benign.
Invitae RCV000045720 SCV000073733 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-04 criteria provided, single submitter clinical testing
Mendelics RCV000045720 SCV000838895 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000083154 SCV000267827 likely benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000254649 SCV000600843 likely benign not specified 2016-12-19 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759684 SCV000889172 likely benign not provided 2018-06-20 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083154 SCV000115228 likely benign Breast-ovarian cancer, familial 2 2013-06-25 no assertion criteria provided clinical testing

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