Assessment of the evidence yield for the calibrated PP3/BP4 computational recommendations.

ABSTRACT:

Purpose

To investigate the number of rare missense variants observed in human genome sequences by ACMG/AMP PP3/BP4 evidence strength, following the ClinGen-calibrated PP3/BP4 computational recommendations.

Methods

Missense variants from the genome sequences of 300 probands from the Rare Genomes Project with suspected rare disease were analyzed using computational prediction tools that were able to reach PP3_Strong and BP4_Moderate evidence strengths (BayesDel, MutPred2, REVEL, and VEST4). The numbers of variants at each evidence strength were analyzed across disease-associated genes and genome-wide.

Results

From a median of 75.5 rare (≤1% allele frequency) missense variants in disease-associated genes per proband, a median of one reached PP3_Strong, 3-5 PP3_Moderate,

SUBMITTER: Stenton SL 

PROVIDER: S-EPMC11560577 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature