ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.507del (p.Phe169fs) (rs587780183)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000116022 SCV000184398 pathogenic Hereditary cancer-predisposing syndrome 2013-09-16 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 RCV000116022 SCV000905463 pathogenic Hereditary cancer-predisposing syndrome 2017-05-26 criteria provided, single submitter clinical testing
GeneDx RCV000254658 SCV000149931 pathogenic not provided 2017-08-21 criteria provided, single submitter clinical testing This pathogenic variant is denoted CHEK2 c.507delT at the cDNA level and p.Phe169LeufsX2 (F169LfsX2) at the protein level. The normal sequence, with the base that is deleted in braces, is CCTT[T]GTAA. The deletion causes a frameshift, which changes a Phenylalanine to a Leucine at codon 169, and creates a premature stop codon at position 2 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. CHEK2 507delT was reported in a breast cancer/sarcoma family (Manoukian 2011), and we consider this variant to be pathogenic.
Invitae RCV000550157 SCV000633194 pathogenic Familial cancer of breast 2018-11-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe169Leufs*2) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs587780183, ExAC 0.001%). This variant has been reported in individuals affected with sarcoma, breast, bladder, and endometrial cancer (PMID: 21562711, 26681312). ClinVar contains an entry for this variant (Variation ID: 128079). 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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