ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1259+1G>C (rs121908707)

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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 RCV000566906 SCV000661796 likely pathogenic Hereditary cancer-predisposing syndrome 2017-07-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Invitae RCV000816882 SCV000957409 pathogenic Familial cancer of breast 2018-12-14 criteria provided, single submitter clinical testing 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. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with non-Hodgkin lymphoma (PMID: 26506619). ClinVar contains an entry for this variant (Variation ID: 126911). Experimental studies have shown that this variant disrupts mRNA splicing (PMID:26506619). 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). For these reasons, this variant has been classified as Pathogenic.
Institute. of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague RCV000114767 SCV000148662 not provided not provided no assertion provided not provided

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