Data-driven insights to inform splice-altering variant assessment.

ABSTRACT: Disease-causing genetic variants often disrupt mRNA splicing, an intricate process that is incompletely understood. Thus, accurate inference of which genetic variants will affect splicing and what their functional consequences will be is challenging, particularly for variants outside of the essential splice sites. Here, we describe a set of data-driven heuristics that inform the interpretation of human splice-altering variants (SAVs) based on the analysis of annotated exons, experimentally validated SAVs, and the currently understood principles of splicing biology. We defined requisite splicing criteria by examining around 202,000 canonical protein-coding exons and 19,000 experimentally validated splicing branchpoints. This analysis defined the sequence, spacing, and motif strength require

SUBMITTER: Sullivan PJ 

PROVIDER: S-EPMC12081236 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature