ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.254C>T (p.Pro85Leu) (rs17883862)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132520 SCV000187617 benign Hereditary cancer-predisposing syndrome 2016-06-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Subpopulation frequency in support of benign classification,Other data supporting benign classification
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513573 SCV000609075 likely benign not provided 2017-05-31 criteria provided, single submitter clinical testing
Color RCV000132520 SCV000684619 benign Hereditary cancer-predisposing syndrome 2014-12-08 criteria provided, single submitter clinical testing
Counsyl RCV000196893 SCV000488524 likely benign Familial cancer of breast 2016-04-25 criteria provided, single submitter clinical testing
GeneDx RCV000120551 SCV000167696 benign not specified 2013-11-27 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.
Genetic Services Laboratory, University of Chicago RCV000120551 SCV000594109 likely benign not specified 2017-01-09 criteria provided, single submitter clinical testing
ITMI RCV000120551 SCV000084705 not provided not specified 2013-09-19 no assertion provided reference population
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000132520 SCV000576431 likely benign Hereditary cancer-predisposing syndrome 2017-02-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000513573 SCV000698792 likely benign not provided 2017-08-09 criteria provided, single submitter clinical testing Variant summary: The CHEK2 c.254C>T (p.Pro85Leu) variant involves the alteration of a non-conserved nucleotide. 2/3 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 143/130972 control chromosomes (1 homozygote) including ExAC, predominantly observed in the African subpopulation at a frequency of 0.007411 (77/10390). This frequency is about 24 times the estimated maximal expected allele frequency of a pathogenic CHEK2 variant (0.0003125), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. This variant has been reported in multiple breast cancer patients without clear evidence supporting causality. Although one functional study showed in vitro kinase actitiy of CHEK2 p.P85L was 40-50% of wild-type CHEK2, two additional functional studies showed this variant does not affect yeast growth rate or in vivo response to DNA damage. In addition, multiple clinical laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant was classified as likely benign.
Invitae RCV000196893 SCV000252812 benign Familial cancer of breast 2018-01-05 criteria provided, single submitter clinical testing
OMIM RCV000005942 SCV000026124 pathogenic Osteosarcoma 2002-01-01 no assertion criteria provided literature only
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000120551 SCV000601163 benign not specified 2016-09-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000513573 SCV000889330 benign not provided 2016-09-21 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.