Katherine R. Chao

This study identifies deep intronic IGHMBP2 variants causing SMARD1 and CMT2S, showing they activate a shared cryptic splice donor, enabling correction with a single antisense oligonucleotide in patient-derived motor neurons.

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 reports two patients with NEB-related congenital myopathy and describes how differential inclusion of NEB exons 143 and 144 affects disease manifestation and MRI patterns.

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

The paper detects and classifies copy number variants in exome data from 6,633 families, identifying causal CNVs in 173 families and improving classification standards.

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.

The paper develops a method to infer compound heterozygosity from exome sequencing data, achieving high accuracy in phasing rare variants for recessive disease diagnosis.

This study evaluates genome sequencing's diagnostic yield in a cohort of undiagnosed rare disease patients, finding it solves 29.3% of cases with specific variant types not detectable by exome sequencing.

The paper performs single-variant and gene-based association analyses of 4,529 phenotypes using exome data from 426,370 UK Biobank individuals, finding associations linked to variant frequency and deleteriousness.

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.

The paper describes the role of the Centers for Mendelian Genomics in advancing gene discovery through data sharing, collaboration, and resource development over the past decade.

The paper introduces MATK, an automated variant ranking tool for Mendelian disease diagnosis, showing it identifies most expert solutions and finds additional variants in unsolved cases.

The paper identifies non-coding variants upstream of MEF2C causing severe developmental disorder through three distinct loss-of-function mechanisms, showing their diagnostic importance in existing exome datasets.

This study identifies genetic mutations in 78% of Diamond-Blackfan anemia patients using whole exome sequencing, finds new RP genes, and reports genotype-phenotype associations.