ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.876del (p.Phe292fs) (rs772683219)

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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 RCV000568161 SCV000669266 pathogenic Hereditary cancer-predisposing syndrome 2017-11-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000215774 SCV000279787 pathogenic not provided 2017-05-10 criteria provided, single submitter clinical testing This deletion of one nucleotide in CHEK2 is denoted c.876delT at the cDNA level and p.Phe292LeufsX12 (F292LfsX12) at the protein level. The normal sequence, with the base that is deleted in brackets, is CTTTTT[delT]GATG. The deletion causes a frameshift, which changes a Phenylalanine to a Leucine at codon 292, and creates a premature stop codon at position 12 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this deletion to be pathogenic.
Invitae RCV000462314 SCV000550473 pathogenic Familial cancer of breast 2018-06-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe292Leufs*12) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with CHEK2-related disease. ClinVar contains an entry for this variant (Variation ID: 234765). Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic.

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