ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.*11C>T

gnomAD frequency: 0.00046  dbSNP: rs200698755
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Preventiongenetics, part of Exact Sciences RCV000249274 SCV000302761 likely benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000370358 SCV000469408 uncertain significance Hyperinsulinism due to glucokinase deficiency 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV000268765 SCV000469409 uncertain significance Transient Neonatal Diabetes, Recessive 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV000326074 SCV000469410 likely benign Maturity-onset diabetes of the young type 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina RCV000383024 SCV000469411 uncertain significance Permanent neonatal diabetes mellitus 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Athena Diagnostics Inc RCV000249274 SCV001476446 benign not specified 2019-09-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000249274 SCV002598566 benign not specified 2022-09-01 criteria provided, single submitter clinical testing Variant summary: GCK c.*11C>T is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.00018 in 273340 control chromosomes (gnomAD), predominantly at a frequency of 0.0016 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 64 fold of the estimated maximal expected allele frequency for a pathogenic variant in GCK causing Monogenic Diabetes (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.*11C>T has been reported in the literature as a polymorphism routinely seen during sequencing of the GCK gene (Osbak_2009). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: one submitter classified the variant as VUS for Hyperinsulinism and likely benign for Maturity Onset Diabetes of the Young, and one submitter classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002463666 SCV002605041 benign Maturity onset diabetes mellitus in young criteria provided, single submitter research Potent mutations in GCK gene is associated with poor secretion of insulin. Its associated with milder forms of diabetes, which can be controlled by diet . However, there is no sufficient evidence to ascertain the significance of rs200698755 in MODY, yet.

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