ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1259+1G>T

dbSNP: rs121908707
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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 RCV000465281 SCV000550499 likely pathogenic Familial cancer of breast 2018-02-07 criteria provided, single submitter clinical testing 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with CHEK2-related disease. ClinVar contains an entry for this variant (Variation ID: 410039). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 11 of the CHEK2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Myriad Genetics, Inc. RCV000465281 SCV004045108 likely pathogenic Familial cancer of breast 2023-06-28 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.

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