ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6937+1G>T (rs886040935)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487394 SCV000567762 uncertain significance not provided 2015-09-01 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6937+1G>T or IVS12+1G>T and consists of a G>T nucleotide substitution at the +1 position of intron 12 of the BRCA2 gene. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing. Although this variant has not, to our knowledge, been published in the literature, it is predicted to cause exon 12 skipping, which has been observed in multiple normal tissues and breast and prostate tumors (Bieche 1999, Li 2009). This variant was not observed in approximately 6,500 individuals of European and African American Ancestry in the NHLBL Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Exclusion of exon 12 results in an in-frame deletion of 32 amino acids. Functional assays of the exon 12-deleted BRCA2 transcript demonstrated no difference in DNA repair functions in comparison to wild type (Li 2009). Although canonical splice variants are typically expected to be pathogenic, the clinical effect of BRCA2 c.6937+1G>T is currently unknown, thus it is unclear whether BRCA2 c.6937+1G>T is pathogenic or benign. We consider it to be a variant of uncertain significance.

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