ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.-39-1G>C

dbSNP: rs1060499566
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001379392 SCV001577188 likely pathogenic Hereditary breast ovarian cancer syndrome 2020-09-09 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 1 of the BRCA2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that disruption of this splice site results in aberrant skipping of exon 2 and aberrant combined skipping of exons 2-3 (PMID: 28905878). Disruption of this splice site has been observed in individual(s) with breast cancer (PMID: 26187060, 28993434, 21520333, Invitae). This variant is not present in population databases (ExAC no frequency).
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV003234794 SCV003932721 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2023-06-06 criteria provided, single submitter clinical testing A likely pathogenic variant in the BRCA2 gene was detected (c.-39-1G>C). This sequence change affects an acceptor splice site in intron 1 of the BRCA2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. A variant affecting the same splicesite (c.-39-1_-39del) has been observed in individuals affected with breast cancer (PMID: 26187060, 28993434), as well as an individual affected with medulloblastoma (PMID: 29753700). ClinVar contains an entry for this variant (Variation ID: 403704). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 28905878), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). Therefore, this variant has been classified as Likely Pathogenic.

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