ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.15G>A (p.Ser5=) (rs145183886)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000858730 SCV000260320 likely benign not provided 2019-03-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000214040 SCV000277654 likely benign Hereditary cancer-predisposing syndrome 2015-08-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
Illumina Clinical Services Laboratory,Illumina RCV000261516 SCV000437730 uncertain significance Colorectal cancer 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000314342 SCV000437731 uncertain significance Neoplasm of the breast 2016-06-14 criteria provided, single submitter clinical testing
Counsyl RCV000204321 SCV000488464 likely benign Familial cancer of breast 2016-04-06 criteria provided, single submitter clinical testing
GeneDx RCV000438041 SCV000518108 likely benign not specified 2017-06-12 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color RCV000214040 SCV000684615 likely benign Hereditary cancer-predisposing syndrome 2016-07-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000438041 SCV000917242 likely benign not specified 2018-10-23 criteria provided, single submitter clinical testing Variant summary: CHEK2 c.15G>A alters a non-conserved nucleotide resulting in a synonymous change. 4/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00013 in 240078 control chromosomes, predominantly within the South Asian subpopulation at a frequency of 0.00046 in the gnomAD database. The observed variant frequency within South Asian control individuals is approximately 1.5-fold above the estimated maximal expected allele frequency for a pathogenic variant in CHEK2 causing Hereditary Breast and Ovarian Cancer phenotype (0.00031), suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.15G>A in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and most classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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