The c.1948G>A (NM_001005361.3(DNM2):c.1948G>A (p.Glu650Lys)) variant in DNM2 is a missense variant predicted to cause substitution of glutamic acid by lysine at amino acid 650. This variant has been reported in 7 probands from 3 families all meeting phenotypic criteria and six having ptosis (PS4; PMIDs: 19623537, 24465259, 31655408). The variant has been reported to segregate with centronuclear myopathy in 4 affected individuals from one family (PP1_Moderate; PMID: 19623537). This variant is absent from gnomAD v4.1 (PM2_Supporting). DNM2, in which the variant was identified, is defined by the ClinGen Congenital Myopathies VCEP as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (PP2). An in-vitro cell culture in muscle cells showed increased GTPase activity indicating that this variant impacts protein function (PMID: 26199319, PS3_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal dominant centronuclear myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: PS4, PP1_Moderate, PP2, PM2_Supporting, PS3_Supporting. (ClinGen Congenital Myopathies VCEP specifications version 1; 8/7/2024)