Submission Details

The CAMK2G gene is located on chromosome 10 at 10q22.2 and encodes the calcium/calmodulin dependent protein kinase II gamma protein which is associated with calcium transport in the sarcoplasmic reticulum in skeletal muscle and may be involved in dendritic and neuronal functioning. CAMK2G was first reported in relation to autosomal dominant syndromic intellectual disability in 2012 (de Ligt et al., PMID 23033978). Two missense variants have been identified in three unrelated heterozygous individuals with de novo inheritance and similar phenotypic presentations (PMIDs: 23033978, 30184290, 35599849). Six additional mutations have been reported in association with intellectual disability in ClinVar (PMID 24234437). Multiple functional studies were done to assess the impact of the Arg292Pro variant, found in two cases, and the results showed an effect on protein stability and nuclear localization (PMID 30184290). A cell culture model using mouse primary hippocampal neurons showed substantial alteration of neuronal morphology in mice transfected with shRNA directed against Camk2g when compared with controls (PMID 30184290). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This gene-disease pair was originally evaluated by the ClinGen Syndromic Disorders Gene Curation Expert Panel on January 6th, 2021. It was reevaluated on October 11th, 2024. As a result of this reevaluation, the classification did not change.