In conclusion, we report a DNAm signature for NCBRS-associated SMARCA2 pathogenic missense variants that can be used to classify VUS in SMARCA2. The DNAm changes in the NCBRS-SMARCA2 DNAm signature occur in genes that represent novel and highly specific targets for future studies to elucidate the molecular pathophysiology of NCBRS and inform the development of targeted therapies, especially with respect to neurodevelopment. The gene discussed is SMARCA2; the disease is intellectual disability-sparse hair-brachydactyly syndrome.