NIPBL and Cornelia de Lange syndrome: Truncation, nonsense, splice site, and frameshifts in NIPBL variants contribute to a truncated and possibly non-functional NIPBL protein pathogenic variant associated with a severe CdLS clinical phenotype; however, missense variants generally result in a milder CdLS pattern, and individuals with large deletions associated with CdLS show more severe clinical symptoms; this grading indicates that NIPBL is sensitive to gene dosage variants (Selicorni et al., 2021).