Creation of an Expert Curated Variant List for Clinical Genomic Test Development and Validation
Year: 2021
Type: article
Abstract: 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. Additionally, it is usually not possible to procure appropriate and characterized genomic DNA reference materials containing the number and scope of variants required. To address these challenges, the Centers for Disease Control and Prevention's Genetic Testing Reference Material Program (GeT-RM) has partnered with the Clinical Genome Resource (ClinGen) to develop a publicly available list of expert curated, clinically important variants. ClinGen Variant Curation Expert Panels nominated 546 variants found in 84 disease-associated genes, including common pathogenic and difficult-to-detect variants. Variant types nominated included 346 single nucleotide variants, 104 deletions, 37 copy number variants, 25 duplications, 18 deletion-insertions, 5 inversions, 4 insertions, 2 complex rearrangements, 3 difficult-to-sequence regions, and 2 fusions. This expert-curated variant list is a resource that provides a foundation for designing comprehensive validation studies and for creating in silico reference materials for clinical genomic test development and validation.
Source: Journal of Molecular Diagnostics
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
Funders: U.S. Department of Health and Human Services, National Institutes of Health, Centers for Disease Control and Prevention, National Human Genome Research Institute, National Institute of Child Health and Human Development, Agency for Toxic Substances and Disease Registry, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1335601273, Expert Panel: Genetics of Malformations of the Central Nervous System, The Clinical Genome Resource - Expert Curation and EHR Integration, Clinical Genome Resource, Primary Mitochondrial Disease Expert Curation Panel, Genomic Clinical Variant Expert Curation Panel for Monogenic Diabetes: A Gateway to Precision Medicine in Diabetes Mellitus, Clinical Genome Resource (ClinGen), Broad-Geisinger Clinical Genome Resource
OpenAlex ID: W3170069791