Samantha M. Baxter

The Rare Genomes Project provides remote genomic sequencing to rare disease families, achieving a 23.3% diagnostic solve rate and highlighting the role of research in overcoming clinical diagnostic barriers.

This study evaluates the diagnostic yield of short-read and long-read sequencing in rare diseases, finding limited added value from long-read sequencing despite increased variant discovery.

This paper estimates the global prevalence of GSD IV and APBD by analyzing GBE1 variants across nine genetic groups, finding 1 in 235,784 individuals are affected.

The paper estimates genetic prevalence for 22 autosomal recessive conditions using gnomAD data and develops a tool to democratize these calculations, highlighting the dynamic nature of prevalence estimates.

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 estimates the genetic prevalence of PLA2G6-associated neurodegeneration using database and literature-based approaches, finding higher prevalence in African/African-American and Asian populations.

The paper develops criteria for identifying, sharing, and reporting novel candidate genes in clinical genomic testing to improve diagnostic yield for Mendelian conditions.

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 paper presents a framework to reduce false positives in predicted loss-of-function variants by analyzing LoF evasion mechanisms and adjusting ACMG/AMP guidelines.

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 presents phenotype and genetic analysis of 206 children with neurodevelopmental disorders from Kenya and South Africa, identifying pathogenic variants in 17% of South African and 38% of Kenyan cases.

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.

Neptune delivers structured genomic data to EHR systems through customizable reports and variant reanalysis, supporting over 15,000 clinical reports.

AutoPVS1 is an automatic tool for PVS1 interpretation of null variants, achieving 95% concordance with manual curation and highlighting variant-specific issues and disease mechanisms.