Poison exon annotations improve the yield of clinically relevant variants in genomic diagnostic testing.

ABSTRACT:

Purpose

Neurodevelopmental disorders (NDDs) often result from rare genetic variation, but genomic testing yield for NDDs remains below 50%, suggesting that clinically relevant variants may be missed by standard analyses. Here, we analyze "poison exons" (PEs), which are evolutionarily conserved alternative exons often absent from standard gene annotations. Variants that alter PE inclusion can lead to loss of function and may be highly penetrant contributors to disease.

Methods

We curated published RNA sequencing data from developing mouse cortex to define 1937 conserved PE regions potentially relevant to NDDs, and we analyzed variants found by genome sequencing in multiple NDD cohorts.

Results

Across 2999 probands, we found 6 novel clinically relevant variants in PE re

SUBMITTER: Felker SA 

PROVIDER: S-EPMC10524927 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature