ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6886A>C (p.Ile2296Leu) (rs576279166)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132216 SCV000187298 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Color RCV000132216 SCV000910979 likely benign Hereditary cancer-predisposing syndrome 2016-11-04 criteria provided, single submitter clinical testing
Counsyl RCV000410842 SCV000488288 uncertain significance Breast-ovarian cancer, familial 2 2016-02-12 criteria provided, single submitter clinical testing
GeneDx RCV000479638 SCV000571484 likely benign not specified 2017-11-21 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.
Illumina Clinical Services Laboratory,Illumina RCV000353391 SCV000383748 likely benign Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000203848 SCV000383749 likely benign Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000479638 SCV000918806 likely benign not specified 2018-01-29 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6886A>C (p.Ile2296Leu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function and the variant is located outside of any known domain or repeat. The observed variant frequency within South Asian control individuals in the gnomAD database (42/30676 chrs) is approximately 1.87 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer phenotype (0.00075), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.6886A>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant as VUS/Likely Benign. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000203848 SCV000261976 likely benign Hereditary breast and ovarian cancer syndrome 2018-01-03 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000132216 SCV000787946 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-05 no assertion criteria provided clinical testing

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