Sharon E. Plon

The paper describes international workshops training variant scientists on the ClinGen Variant Curation Interface (VCI) and reports on its usage and costs.

This study quantifies how patient-level factors and site-level practices affect diagnostic yield in exome and genome sequencing across five clinical sites.

The paper develops a comprehensive list of genetic conditions for genomic newborn screening, including 777 conditions associated with 743 genes, for implementation across multiple U.S. states and territories.

The paper compares germline and somatic variants in 40 tumor suppressor genes, finding distinct mutational patterns and locations shaped by different selection pressures.

The paper analyzes somatic NMDe variants in oncogenes and dual-function genes across cancer cohorts, identifying two distinct patterns with different functional consequences.

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

The paper analyzes variant classification disparities between European-like and non-European-like genetic ancestries and shows that MAVE data can reduce these disparities in VUS reclassification.

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

The paper evaluates the pathogenicity of intronic and synonymous variants using splicing prediction algorithms and in vitro assays, identifying potentially disease-causing variants previously classified as benign.

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

The paper introduces the ClinGen Variant Curation Interface, a platform for applying ACMG/AMP guidelines to classify genetic variants, enabling collaboration and standardization in clinical variant interpretation.

The paper updates CDH1 variant curation guidelines to resolve conflicting interpretations and reduce variants of uncertain significance for clinical use.

The paper specifies TP53-specific ACMG/AMP variant classification guidelines, reducing variants of uncertain significance from 28% to 12%.

The paper highlights the lack of standard definitions and protocols for collecting and using race, ethnicity, and ancestry data in clinical genetics and precision medicine.

The paper identifies ancestry-specific germline variants in cancer predisposition genes and their somatic effects across diverse populations.

The paper analyzes REA data collection practices and disparities in gnomAD, highlighting the need for standardized frameworks to improve diversity and variant interpretation in clinical genomics.

The paper develops ADmiRE to annotate miRNA variants in large population datasets, identifies highly constrained miRNAs, and provides conservation scores for future disease studies.

The paper evaluates in silico algorithms for ACMG/AMP variant classification, finding high-performing algorithms and combinations that improve concordance.

The paper presents a framework to evaluate the clinical validity of gene-disease associations, validated using representative gene-disease pairs.