Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| National Newborn Screening Laboratory, |
RCV002227433 | SCV002506590 | likely pathogenic | Maturity-onset diabetes of the young type 2 | criteria provided, single submitter | clinical testing | This is a missense variant located within exon 5 and generates a change from the aminoacid Glycine to Aspartic acid in position 162. It is located in a mutational hot spot (PM1). It is not present in population databases (GnomAD exomes, GnomAD genomes) (PM2). it is a missense change at an amino acid residue where a different missense change determined to be pathogenic (c.484G>A) (PM5). Multiple lines of computational evidence support a deleterious effect on the gene (PP3). Missense variant in a gene that has a low rate of benign missense variation for which missense variants are a common mechanism of a disease (PP2). This variant has been reported in the literature associated with individuals with MODY2 (PMID: 19790256 18382660) | |
| Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV002227433 | SCV005326358 | pathogenic | Maturity-onset diabetes of the young type 2 | criteria provided, single submitter | clinical testing | The p.Gly162Asp substitutes the glycine at amino acid 162 with aspartic acid. In silico tools predict this variant is damaging; it is two nucleotides away from the exon-intron boundary and could result in altered mRNA splicing. This variant has previously been reported in several unrelated individuals with GCK-related maturity-onset diabetes of the young (GCK-MODY, MIM: 125851) (PMID: 18382660, PMID: 19790256, PMID: 36257325). This variant is absent from large population studies (gnomAD v4.0.0). Other variants at this amino acid position have also been reported in affected individuals (PMID: 18382660, PMID: 31291970). |