ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.670+1del (rs886040922)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000258378 SCV000326377 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000590865 SCV000700078 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-24 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000690232 SCV000817911 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-03-19 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the BRCA1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 267611). Experimental studies have shown that this change results in the generation of an aberrant transcript that leads to the in-frame activation of a cryptic donor splice site in exon 9, located 1 nucleotide upstream of the natural splice site (PMID: 24667779). However, an in-frame BRCA1 isoform that skips exons 8 and 9 (also known as exons 9 and 10) is naturally expressed in normal blood and breast tissue, suggesting that this splice donor variant may not be deleterious (PMID: 24569164). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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