Investigation of cryptic JAG1 splice variants as a cause of Alagille syndrome and performance evaluation of splice predictor tools.

ABSTRACT: Haploinsufficiency of JAG1 is the primary cause of Alagille syndrome (ALGS), a rare, multisystem disorder. The identification of JAG1 intronic variants outside of the canonical splice region as well as missense variants, both of which lead to uncertain associations with disease, confuses diagnostics. Strategies to determine whether these variants affect splicing include the study of patient RNA or minigene constructs, which are not always available or can be laborious to design, as well as the utilization of computational splice prediction tools. These tools, including SpliceAI and Pangolin, use algorithms to calculate the probability that a variant results in a splice alteration, expressed as a Δ score, with higher Δ scores (>0.2 on a 0-1 scale) positively correlated with aberrant splicin

SUBMITTER: Keefer-Jacques E 

PROVIDER: S-EPMC11440345 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature