Leslie G. Biesecker

Genetics of growth rate in induced pluripotent stem cells

The paper identifies genetic factors influencing iPSC growth rates, finding rare variants in WDR54 and a polygenic background explaining most variance.

Specification of frequency criteria for secondary findings genes to improve variant classification concordance

The paper establishes frequency criteria for secondary findings genes to improve variant classification consistency by setting disease allele frequency thresholds for 58 monogenic disease entities.

Direct RNA nanopore sequencing reveals rapid RNA modification changes following glucose stimulation of human pancreatic beta-cell lines

The paper uses direct RNA nanopore sequencing to identify RNA modification changes in human pancreatic beta-cells after glucose stimulation, finding 1,697 differentially modified sites linked to type 2 diabetes genes.

Calibration of additional computational tools expands ClinGen recommendation options for variant classification with PP3/BP4 criteria

The paper calibrates three new computational tools for clinical variant classification, finding they provide evidence strength comparable to previously recommended tools.

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

The paper assesses rare missense variants in genome sequences using PP3/BP4 evidence strength classifications and finds few variants meet strong or moderate criteria.

Evidence-based calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for clinical use of PP3/BP4 criteria

The paper calibrates computational tools for missense variant pathogenicity classification and provides evidence-based revisions to PP3/BP4 ACMG/AMP criteria.

Updated Variant Curation Expert Panel Criteria and Pathogenicity Classifications for 251 Variants for RYR1-related Malignant Hyperthermia Susceptibility

The paper updates ACMG/AMP criteria for RYR1-related MHS and classifies 251 variants, finding that many VUS classifications lack sufficient evidence and suggesting functional studies are needed.

Genetic regulation of OAS1 nonsense-mediated decay underlies association with risk of severe COVID-19

The paper identifies a Neandertal introgressed haplotype in the OAS1 gene associated with increased risk of severe COVID-19 and shows it impairs SARS-CoV-2 clearance through genetic regulation of OAS1 expression.

Evaluating the impact of in silico predictors on clinical variant classification

This study evaluates how in silico predictors influence clinical variant classification, finding that PP3 and BP4 criteria are frequently applied and often affect variant classifications.

Variant Curation Expert Panel Recommendations for RYR1 Pathogenicity Assertions in Malignant Hyperthermia Susceptibility

The paper develops and validates ACMG/AMP criteria for assessing RYR1 variant pathogenicity in malignant hyperthermia, using quantitative calibration and expert panel evaluation.

Recommendations for application of the functional evidence PS3/BS3 criterion using the ACMG/AMP sequence variant interpretation framework

The paper provides structured recommendations for applying the PS3/BS3 functional evidence criteria in variant interpretation using the ACMG/AMP framework, including a four-step framework and minimum control requirements.

Recommendations for Interpreting the Loss of Function PVS1 ACMG/AMP Variant Criteria

The paper provides refined recommendations for applying the PVS1 ACMG/AMP variant criteria to loss of function variants, addressing gaps in the original guideline through evaluation with curated variants.