A gene pathogenicity tool "GenePy" identifies missed biallelic diagnoses in the 100,000 Genomes Project.

ABSTRACT:

Purpose

The 100,000 Genomes Project diagnosed a quarter of affected participants, but 26% of diagnoses were not on the applied gene panel(s); with many being de novo variants. Assessing biallelic variants without a gene panel is more challenging.

Methods

We sought to identify missed biallelic diagnoses using GenePy, which incorporates allele frequency, zygosity, and a user-defined deleterious metric, generating an aggregate GenePy score per gene, per participant. We calculated GenePy scores for 2862 recessive disease genes in 78,216 100,000 Genomes Project participants. For each gene, we ranked participant GenePy scores and scrutinized affected participants without a diagnosis, whose scores ranked among the top 5 for each gene. In cases which participant phenotypes overlappe

SUBMITTER: Seaby EG 

PROVIDER: S-EPMC11771214 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature