Combined Bioinformatic and Splicing Analysis of Likely Benign Intronic and Synonymous Variants Reveals Evidence for Pathogenicity.

ABSTRACT:

Background

Current clinical variant analysis pipelines focus on coding variants and intronic variants within 10-20 bases of an exon-intron boundary that may affect splicing. The impact of newer splicing prediction algorithms combined with in vitro splicing assays on rare variants currently considered Benign/Likely Benign (B/LB) is unknown.

Methods

Exome sequencing data from 576 pediatric cancer patients enrolled in the Texas KidsCanSeq study were filtered for intronic or synonymous variants absent from population databases, predicted to alter splicing via SpliceAI (>0.20), and scored as potentially deleterious by CADD (>10.0). Total cellular RNA was extracted from monocytes and RT-PCR products analyzed. Subsequently, rare synonymous or intronic B/LB variants in a subs

SUBMITTER: Hirschi OR 

PROVIDER: S-EPMC10635218 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature