Systematic identification of disease-causing promoter and untranslated region variants in 8040 undiagnosed individuals with rare disease.

ABSTRACT:

Background

Both promoters and untranslated regions (UTRs) have critical regulatory roles, yet variants in these regions are largely excluded from clinical genetic testing due to difficulty in interpreting pathogenicity. The extent to which these regions may harbour diagnoses for individuals with rare disease is currently unknown.

Methods

We present a framework for the identification and annotation of potentially deleterious proximal promoter and UTR variants in known dominant disease genes. We use this framework to annotate de novo variants (DNVs) in 8040 undiagnosed individuals in the Genomics England 100,000 genomes project, which were subject to strict region-based filtering, clinical review, and validation studies where possible. In addition, we performed region and vari

SUBMITTER: Martin-Geary AC 

PROVIDER: S-EPMC11998461 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature