Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003493416 | SCV004242364 | uncertain significance | Monogenic diabetes | 2024-01-18 | reviewed by expert panel | curation | The c.322T>G variant in the glucokinase gene,GCK, causes an amino acid change of tyrosine to aspartic acid at codon 108 (p.(Tyr108Asp)) of NM_000162.5. GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.967, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been reported as likely pathogenic in ClinVar; however, no clinical information was provided (ClinVar ID: 36212). Another missense variant, c.322T>C p.Tyr108His,has been interpreted as pathogenic by the ClinGen MDEP, and p.Tyr108Asp has a greater Grantham distance (PM5). In summary, c.322T>G meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): PM5, PP2, PP3, PM2_Supporting. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000029875 | SCV000052530 | likely pathogenic | Maturity-onset diabetes of the young type 2 | 2011-08-18 | criteria provided, single submitter | curation | Converted during submission to Likely pathogenic. |
Clinical Genomics, |
RCV002463998 | SCV002605309 | 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 rs193922292 in MODY, yet. |