Background
• RNA sequencing (RNAseq) can provide crucial functional data for accurate interpretation of diagnostic genome sequencing (GS) results.
• Here, we describe a patient with macrocephaly and global developmental delay (DD) who was found to carry a familial intronic variant in the CHD3 gene, originally classified as a variant of uncertain significance (VUS).
• Pathogenic variants in CHD3 are associated with Snijders Blok-Campeau syndrome (SNIBCPS), an autosomal
dominant neurodevelopmental disorder characterized by global DD, intellectual disability (ID), hypotonia,
delayed speech acquisition, and dysmorphic features.
• Clinically validated RNAseq on this VUS upgraded its classification to likely pathogenic (LP). This provided impactful diagnostic information for the patient and family.
