Submissions for variant NM_000162.5(GCK):c.718A>G (p.Asn240Asp)

dbSNP: rs1562715574

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Translational Genomics Laboratory, University of Maryland School of Medicine	RCV000754808	SCV000882457	likely pathogenic	Maturity-onset diabetes of the young type 2	2017-06-08	criteria provided, single submitter	clinical testing	The c.718A>G variant in codon 240 (exon 7) of the glucokinase gene, GCK, results in the substitution of Asparagine to Aspartic Acid. The c.718A>G was not observed in the NHLBI Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium databases; however, this variant has been reported to segregate with diabetes in a family (father and two sons) with a clinical picture consistent with Maturity-Onset Diabetes of the Young, Type 2 (MODY2, also called GCK-MODY) (24735133). This residue is important for H-bonding within the protein and alteration is predicted to disrupt the tertiary structure of the protein (24735133;18382660). Additionally, multiple lines of computational evidence (LRT, MutationTaster, FATHMM, MetaSVM, MetaLR, CADD, GERP, PROVEAN) predict this variant is probably damaging to the protein structure, function, or protein-protein interaction. In addition, the personal and family history for this case is highly suggestive of GCK-MODY.ACMG criteria = PM1, PM2, PP1, PP3
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002463738	SCV002605112	uncertain risk allele	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 rs1562715574 in MODY, yet.