Publications by authors named "Emma Wilcox"
Purpose: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not.
Methods: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship.
Article Synopsis
- In silico evidence is used by ACMG/AMP guidelines to assess the pathogenicity of genetic variants, specifically through the PP3 and BP4 criteria, but their effects on variant classification were not well understood.
- A study analyzed 727 missense variants to see how frequently PP3 and BP4 were applied, discovering they were used in 55% of cases and altered classifications in 15% of those instances.
- The results indicate that in silico criteria significantly influence variant classification outcomes and suggest that established thresholds can allow PP3 and BP4 to be regarded as moderate strength evidence.
Modern genomic sequencing tests often interrogate large numbers of genes. Identification of appropriate reference materials for development, validation studies, and quality assurance of these tests poses a significant challenge for laboratories. It is difficult to develop and maintain expert knowledge to identify all variants that must be validated to ensure analytic and clinical validity.
View Article and Find Full Text PDFPurpose: The ClinGen Variant Curation Expert Panels (VCEPs) provide disease-specific rules for accurate variant interpretation. Using the hearing loss-specific American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines, the Hearing Loss VCEP (HL VCEP) illustrates the utility of expert specifications in variant interpretation.
Methods: A total of 157 variants across nine HL genes, previously submitted to ClinVar, were curated by the HL VCEP.