Submissions for variant NM_000162.5(GCK):c.364-18A>G

gnomAD frequency: 0.00118  dbSNP: rs191255582

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000616972	SCV000726118	likely benign	not specified	2017-12-28	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.
Athena Diagnostics	RCV000711771	SCV000842167	benign	not provided	2017-09-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000711771	SCV002409882	benign	not provided	2024-12-07	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002464027	SCV002605277	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 rs191255582 in MODY, yet.
Fulgent Genetics, Fulgent Genetics	RCV002506472	SCV002807137	benign	Type 2 diabetes mellitus; Hyperinsulinism due to glucokinase deficiency; Maturity-onset diabetes of the young type 2; Permanent neonatal diabetes mellitus 1	2021-08-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000616972	SCV005887894	benign	not specified	2025-01-08	criteria provided, single submitter	clinical testing	Variant summary: GCK c.364-18A>G alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing (TrAP). However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00031 in 250628 control chromosomes, predominantly at a frequency of 0.0039 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 156 fold of the estimated maximal expected allele frequency for a pathogenic variant in GCK causing Monogenic Diabetes phenotype (2.5e-05). c.364-18A>G has been reported in the literature in at least one individual affected with non-insulin-dependent diabetes mellitus (Stoffel_1993). These report(s) do not provide unequivocal conclusions about association of the variant with Monogenic Diabetes. The following publication have been ascertained in the context of this evaluation (PMID: 8495817). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 514377). Based on the evidence outlined above, the variant was classified as benign.