Michael W. Wilson

gnomAD v4 (730,947 exomes) brings LOFTEE-2 loss-of-function annotation (0.90 precision, strict mode), missense-aware constraint, and LLM-mined literature evidence combined with constraint to rank disease genes.

The paper analyzes over 800,000 human genomes to assess penetrance of clinically relevant variants, finding that 95% of pLoF variants in severe diseases have explanations for lack of disease manifestation.

This paper improves allele frequency estimates in gnomAD by applying local ancestry inference to admixed populations, revealing significant frequency differences that could affect clinical interpretation.

The paper harmonizes diverse human genomes from multiple datasets to create a new reference panel with improved variant coverage and population structure analysis.

The paper evaluates variant prioritization methods for rare disease diagnosis using data from the Rare Genomes Project, finding that top models identify causal variants in most solved families and uncover potential candidates in unsolved ones.

The paper quantifies regional missense mutational intolerance using 730,947 exomes to identify constrained gene regions and improve variant interpretation.

Rare-variant depletion in 1kb windows of 76,156 gnomAD genomes, versus feature-adjusted mutation expectations, marks regulatory elements and outperforms seven alternative scores at flagging functional non-coding variants.

seqr is a web-based tool for analyzing rare disease genomic data, enabling variant filtering, annotation, and collaboration, with over 10,000 families analyzed and 300 novel disease genes discovered.