ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.920dup (p.Glu308fs) (rs786203053)

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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 RCV000166190 SCV000216967 pathogenic Hereditary cancer-predisposing syndrome 2018-04-09 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 RCV000483271 SCV000571010 pathogenic not provided 2018-05-11 criteria provided, single submitter clinical testing This duplication of one nucleotide in CHEK2 is denoted c.920dupG at the cDNA level and p.Glu308ArgfsX4 (E308RfsX4) at the protein level. The normal sequence, with the base that is duplicated in brackets, is AGGGG[dupG]AGAG. The duplication causes a frameshift which changes a Glutamic Acid to an Arginine at codon 308, and creates a premature stop codon at position 4 of the new reading frame. CHEK2 920dupG has been observed in individuals with breast cancer (Decker 2017). We consider this variant to be pathogenic.
Invitae RCV000635824 SCV000757248 pathogenic Familial cancer of breast 2018-10-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu308Argfs*4) 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 been observed in an individual affected with breast cancer (PMID: 28779002). ClinVar contains an entry for this variant (Variation ID: 186573). 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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