ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.875_876del (p.Phe291_Phe292insTer) (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 RCV000219196 SCV000275231 pathogenic Hereditary cancer-predisposing syndrome 2015-04-22 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 RCV000255563 SCV000322482 pathogenic not provided 2018-09-12 criteria provided, single submitter clinical testing This deletion of two nucleotides is denoted CHEK2 c.875_876delTT at the cDNA level and p.Phe292Ter (F292X) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CTTTT[delTT]GATG. The deletion creates a nonsense variant, which changes a Phenylalanine to a premature stop codon. 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. We consider this variant to be pathogenic.
Invitae RCV000635697 SCV000757118 pathogenic Familial cancer of breast 2017-10-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe292*) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CHEK2-related disease. ClinVar contains an entry for this variant (Variation ID: 231395). 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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