The Clinical Genome Resource (ClinGen) is a valuable initiative funded by the National Institutes of Health (NIH) aimed at clarifying the clinical significance of genes and their variants. Recently, ClinGen has released information on over 2,700 genes that have been carefully selected for their connection to genetic disorders, such as cancer, cardiovascular diseases, and neurodevelopmental conditions. An article in the journal Genetics in Medicine, the official publication of the American College of Medical Genetics and Genomics (ACMG), outlines the genomic curation methods and the necessary software and infrastructure developed to support the ClinGen global consortium in conducting extensive, evidence-based curation.
The ClinGen consortium was originally formed in 2013 by the National Human Genome Research Institute and now includes more than 2,500 expert members from 69 countries and regions. These specialists are organized into over 100 disease-specific panels that identify genes associated with diseases, determine which variants are responsible for causing these diseases, and clarify when medical interventions are warranted. The consortium’s mission is to standardize the evaluation and curation of genomic information for application in medical practices and research.
The outcomes of these initiatives are accessible to the public at www.clinicalgenome.org. All curated variants are also included in the ClinVar database and the ClinGen Evidence Repository, while all curated genes are available in the GenCC database. According to the paper, as of January 2024, ClinGen experts have confirmed 2,420 gene-disease relationships, evaluated 1,557 genes for dosage sensitivity, and assessed actionability for 447 gene-condition pairs in both pediatric and adult contexts. Researchers have also categorized 5,161 unique pathogenic variants, with these figures continuing to rise.
“The ClinGen resource provides a solid, open-access platform that aids genomic interpretation in clinical settings and research laboratories globally,” stated Dr. Sharon Plon, the corresponding author, co-principal investigator for the Baylor ClinGen project, and professor of molecular and human genetics and pediatrics — hematology and oncology at Baylor. “The genomic insights produced by our consortium can be utilized to create evidence-based genetic testing panels, address inconsistencies in variant classification, and assist in communicating genomic findings to patients.”
Research at Baylor emphasizes the development of software infrastructure and computational methods to broaden the existing work, increase the number of genes in the resource, and enhance integration into healthcare provision. Baylor also spearheads research on hereditary cancer genes.
“The software engineering team at the Baylor Bioinformatics Research Laboratory has developed crucial computational infrastructure for this project, including the Clingen Allele Registry, Criteria Specification Registry, and the Linked Data Hub. These microservices centered around application programming interfaces (APIs) represent innovative progress in academic software development, ensuring that ClinGen knowledge is findable, accessible, interoperable, and reusable,” explained Dr. Aleksandar Milosavljevic, co-principal investigator of the Baylor ClinGen project, director of the Bioinformatics Research Laboratory, and holder of the Henry and Emma Meyer Professorship in Molecular Genetics at Baylor.
Plon serves as the Dan L Duncan Comprehensive Cancer Center Professorship holder at Baylor and is also the co-leader of the pediatric cancer program at the Duncan Cancer Center as well as the director of the Cancer Genetics and Genomics Program at Texas Children’s Hospital. Milosavljevic leads the Program in Quantitative and Computational Biosciences, is co-director of the Computational and Integrative Biomedical Research Center, and is a member of the Dan L Duncan Comprehensive Cancer Center at Baylor.
This research is primarily funded by the National Human Genome Research Institute and the National Cancer Institute (U24HG006834, U24HG009650, and U24HG009649), along with support from the NIH Intramural Research program.
