ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.219A>G (p.Leu73=)

dbSNP: rs876659123
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000494869 SCV000578289 likely benign Breast-ovarian cancer, familial, susceptibility to, 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics RCV000218348 SCV000275205 likely benign Hereditary cancer-predisposing syndrome 2015-04-14 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV000459369 SCV000560301 likely benign Hereditary breast ovarian cancer syndrome 2023-12-04 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000218348 SCV000688372 likely benign Hereditary cancer-predisposing syndrome 2017-07-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193766 SCV001362861 likely benign not specified 2019-05-06 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.219A>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251106 control chromosomes (gnomAD). 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.219A>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters, including one expert panel have provided clinical-significance assessments for this variant in ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Brotman Baty Institute, University of Washington RCV000494869 SCV001238488 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro

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