ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.58C>T (p.Gln20Ter) (rs536907995)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255024 SCV000322541 likely pathogenic not provided 2018-05-24 criteria provided, single submitter clinical testing This variant is denoted CHEK2 c.58C>T at the cDNA level and p.Gln20Ter (Q20X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been identified in several breast cancer patients, one of whom also had ovarian cancer and was found to harbor a BRCA2 pathogenic variant (Foley 2015, Baloch 2016, Sun 2017, Fan 2018). In a case-control study, CHEK2 Gln20Ter was identified 0/13,087 breast cancer cases and 1/5,488 controls (Decker 2017). Additionally, this variant was observed in 1/50 healthy Central Asian individuals undergoing whole genome sequencing (Bodian 2014). Of note, the participants in this study were younger than 50 years old thus the unaffected status of this individual may not be significant. Based on currently available evidence, we consider CHEK2 Gln20Ter to be a likely pathogenic variant.
Invitae RCV000458969 SCV000550527 pathogenic Familial cancer of breast 2019-11-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln20*) in the CHEK2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs536907995, ExAC 0.09%). This variant has been reported in individuals affected with breast and ovarian cancer (PMID: 26023681, 27039729). ClinVar contains an entry for this variant (Variation ID: 133887). Loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000458969 SCV000677811 pathogenic Familial cancer of breast 2017-06-05 criteria provided, single submitter clinical testing
Color RCV000579628 SCV000684663 likely pathogenic Hereditary cancer-predisposing syndrome 2019-09-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000579628 SCV001186719 pathogenic Hereditary cancer-predisposing syndrome 2017-10-10 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
ITMI RCV000120552 SCV000084706 not provided not specified 2013-09-19 no assertion provided reference population

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