Fig. 1: Curation of pLoF variants in haploinsufficient disease genes found in gnomAD reveals transcript errors as a major confounding error mode in variant annotation.
From: Transcript expression-aware annotation improves rare variant interpretation
We identified and manually curated 401 pLoF variants in the gnomAD dataset in 61 haploinsufficient severe developmental delay genes and flagged any reason the pLoF may not be a true LoF variant. Top, the frequency of each error mode present in the 306 variants classified as unlikely to be a true LoF. Transcript errors emerge as a major putative error mode in the annotation of these pLoF variants. Bottom, bee swarm plot shows the average pext score across GTEx tissues for each variant in the error categories. This shows that pext values are discriminately lower for variants that are annotated as possible transcript errors (P = 4.1 × 10−38, two-sided Wilcoxon test between transcript errors and other error modes).
