ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.302-5T>C (rs778668665)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218881 SCV000274541 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-04 criteria provided, single submitter clinical testing The c.302-5T>C intronic variant results from a T to C substitution 5 nucleotides upstream from coding exon 5 in the BRCA1 gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Health, Inc RCV000218881 SCV001348057 likely benign Hereditary cancer-predisposing syndrome 2020-03-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193803 SCV001362921 uncertain significance not specified 2019-10-24 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.302-5T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant to slightly weaken a 3' acceptor site. However, the variant was shown to have no impact on splicing based on patient mRNA (Leman_2018, Gelli_2019). The variant was absent in 250406 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.302-5T>C has been reported in the literature in an individual affected with Hereditary Breast and Ovarian Cancer (Manguoglu_2010). This report does not provide an unequivocal conclusion about association of the variant with Hereditary Breast and Ovarian Cancer. A ClinVar submission (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as a VUS - possibly benign variant.

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