Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003234538 | SCV003932645 | pathogenic | Monogenic diabetes | 2023-05-26 | reviewed by expert panel | curation | The c.483G>A variant in the glucokinase gene, GCK, is a synonymous (silent) variant at codon 161 (p.(Lys161=)) of NM_000162.5. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). It is predicted by SpliceAI to impact splicing (SpliceAI score of 0.85 for donor gain and 0.52 for donor loss, which are greater than the MDEP cutoff of 0.2) (PP3), and there is evidence from RNA studies that this variant results in aberrant splicing, indicating that this variant impacts protein function (PS3; Internal lab contributor). This variant was identified in five unrelated individuals with mildly elevated HbA1c that did not require treatment, and segregated with the phenotype, with four informative meioses in three families (PS4_Moderate, PP1_Strong; PMID: 1956454, Internal lab contributors). In summary, c.483G>A meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP VCEP (specification version 1.1, approved 3/23/23): PM2_Supporting, PP3, PS4_Moderate, PP1_Strong, PS3. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000029887 | SCV000052542 | 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, |
RCV002464001 | SCV002605242 | likely 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 rs193922302 in MODY, yet. | |
Athena Diagnostics Inc | RCV003482231 | SCV004229663 | pathogenic | not provided | 2023-08-29 | criteria provided, single submitter | clinical testing | This variant has been identified in multiple unrelated individuals with clinical features associated with this gene and appears to segregate with disease in at least one family. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Assessment of experimental evidence suggests this variant results in abnormal protein function. (Personal communication related to ClinVar ID: 36224, Accession: SCV003932645.1) |