Fig. 1.

Schematics of a splicing event, the two types of spliceosome, and typical consequences of a BP variant. (A) Schematic of the biological processes of transcription, splicing, and translation from DNA to pre-mRNA to mature mRNA and protein. In pre-mRNA splicing, the BP is first recognized, two exons are then joined, and the intervening intron is finally released as a circular lariat. (B) Schematic of the major (U2-type, on the left) and minor (U12-type, on the right) spliceosomes, with an illustration of the interaction between pre-mRNA sequence and U2/U12 snRNA. (C) Schematic of the potential molecular consequences of a BP variant, including complete/partial exon skipping and complete/partial intron retention. The percentage in parentheses refer to the observed fraction of each category from the published pathogenic BP variants (note that one variant could result in more than one missplicing consequence).