ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.1501G>A (p.Glu501Lys) (rs17883172)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160440 SCV000210994 uncertain significance not provided 2018-01-25 criteria provided, single submitter clinical testing This variant is denoted CHEK2 c.1501G>A at the cDNA level, p.Glu501Lys (E501K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAG>AAG). This variant was observed in four BRCA1/2-negative Pakistani individuals with a personal history of breast and/or ovarian cancer and absent in 150 healthy female controls, but the authors considered it benign based on in silico analyses (Rashid 2013). This variant, denoted Glu544Lys using an alternate reference sequence (NP_001005735.1), has also been reported in an individual with chondroblastic osteosarcoma (Ballinger 2016). Although this variant was observed in large population cohorts, population data in this region of CHEK2 are not considered reliable due to high pseudogene homology (Lek 2016). CHEK2 Glu501Lys is located in the kinase domain (Cai 2009, Roeb 2012). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether CHEK2 Glu501Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000160440 SCV000259637 likely benign not provided 2019-02-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000213437 SCV000276094 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000205886 SCV000488577 uncertain significance Familial cancer of breast 2016-05-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160440 SCV000888109 uncertain significance not provided 2018-01-25 criteria provided, single submitter clinical testing
Color RCV000213437 SCV000910698 likely benign Hereditary cancer-predisposing syndrome 2015-04-24 criteria provided, single submitter clinical testing

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