ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.209-8G>A (rs144798843)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000249810 SCV000594939 likely benign not specified 2017-06-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000302206 SCV000469444 likely benign Hyperinsulinism, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000359365 SCV000469445 likely benign Permanent neonatal diabetes mellitus 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000266999 SCV000469446 likely benign Transient Neonatal Diabetes, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000305726 SCV000469447 likely benign Maturity onset diabetes mellitus in young 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000249810 SCV000052526 benign not specified 2018-09-06 criteria provided, single submitter clinical testing Variant summary: GCK c.209-8G>A alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 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 0.0025 in 277376 control chromosomes, predominantly at a frequency of 0.0047 within the Non-Finnish European subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 188 fold of the estimated maximal expected allele frequency for a pathogenic variant in GCK causing Maturity Onset Diabetes of the Young 2/Neonatal Diabetes Mellitus phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.209-8G>A has been reported in the literature in individuals affected with Maturity Onset Diabetes of the Young 2/Neonatal Diabetes Mellitus, however in at least one family the variant did not segregate with disease (Neu_2001). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics RCV000249810 SCV000302764 likely benign not specified criteria provided, single submitter clinical testing

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