ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.63A>G (p.Lys21=)

dbSNP: rs1280004443
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506652 SCV000600699 uncertain significance not specified 2016-12-06 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001190707 SCV001358283 likely benign Hereditary cancer-predisposing syndrome 2019-02-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001449216 SCV001652327 likely benign Hereditary breast ovarian cancer syndrome 2024-12-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000506652 SCV002103952 likely benign not specified 2022-02-03 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.63A>G alters a non-conserved nucleotide resulting in a synonymous change. 4/4 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 251130 control chromosomes. 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.63A>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome 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 with conflicting assessments. Based on the evidence outlined above, the variant was classified as likely benign.
All of Us Research Program, National Institutes of Health RCV004802109 SCV005424231 likely benign BRCA2-related cancer predisposition 2024-06-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV001190707 SCV005552927 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-06 criteria provided, single submitter clinical testing The c.63A>G variant (also known as p.K21K), located in coding exon 1 of the BRCA2 gene, results from an A to G substitution at nucleotide position 63. This nucleotide substitution does not change the lysine at codon 21. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Based on the available evidence, the clinical significance of this variant remains unclear.
3DMed Clinical Laboratory Inc RCV000677832 SCV000803992 uncertain significance Breast neoplasm 2017-04-21 no assertion criteria provided clinical testing

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