ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.277del (p.Trp93fs) (rs786203458)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166773 SCV000217586 pathogenic Hereditary cancer-predisposing syndrome 2017-08-22 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)
Color RCV000166773 SCV000684623 pathogenic Hereditary cancer-predisposing syndrome 2016-06-13 criteria provided, single submitter clinical testing
Counsyl RCV000197766 SCV000488948 pathogenic Familial cancer of breast 2016-08-04 criteria provided, single submitter clinical testing
GeneDx RCV000223102 SCV000279224 pathogenic not provided 2018-04-11 criteria provided, single submitter clinical testing This deletion of one nucleotide in CHEK2 is denoted c.277delT at the cDNA level and p.Trp93GlyfsX17 (W93GfsX17) at the protein level. The normal sequence, with the base that is deleted in brackets, is GCCCCC[delT]GGGC. The deletion causes a frameshift, which changes a Tryptophan to a Glycine at codon 93, and creates a premature stop codon at position 17 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in at least one patient with breast cancer and additional individuals undergoing multi-gene panel testing (Leedom 2016, Lhota 2016). Based on the currently available evidence, we consider this variant to be pathogenic.
Invitae RCV000197766 SCV000253900 pathogenic Familial cancer of breast 2018-12-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp93Glyfs*17) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. This variant has been reported in an individual affected with breast cancer (PMID: 26822949). ClinVar contains an entry for this variant (Variation ID: 187085). 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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