ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.792+2T>C (rs545982789)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570644 SCV000669261 likely pathogenic Hereditary cancer-predisposing syndrome 2018-01-03 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 RCV000205137 SCV000261050 likely pathogenic Familial cancer of breast 2018-04-29 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 6 of the CHEK2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs545982789, ExAC 0.001%). This variant has not been reported in the literature in individuals with CHEK2-related disease. ClinVar contains an entry for this variant (Variation ID: 220480). 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). 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.

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