Skip Navigation
NIH

The Clinical Genome (ClinGen) Resource

ClinGen logo

 

Background

Medical and research centers are increasingly sequencing exomes or whole genomes of patients. However, identifying sequence variants relevant to disease is difficult.  As a result, information on few genomic variants is used in clinical practice. One factor that limits the clinical use of variant information is the lack of an openly accessible knowledge base that captures genetic variants, their phenotypic and functional effects, and other clinical information. The Clinical Genome Resource (ClinGen) aims to collect phenotypic and clinical information on variants across the genome, develop a consensus approach to identify clinically relevant genetic variants, and disseminate information about the variants to researchers and clinicians.  This resource is essential for advancing the goals of implementing genomics in clinical care and will improve the understanding of phenotypic and functional effects of genetic variants and their clinical value.
 
ClinGen investigators are developing standard approaches for sharing genomic and phenotypic data provided by clinicians, researchers, and patients through centralized databases, such as ClinVar, and are working to standardize the clinical annotation and interpretation of genomic variants.  Working groups are implementing evidence-based expert consensus methods to curate the clinical validity and medical actionability of genes and variants.   Experts in the areas of cardiovascular disease, pharmacogenomics, hereditary (germline) cancer, somatic cancer, and inborn errors of metabolism have been brought together to assist in these curation efforts.  ClinGen also aims to develop machine-learning algorithms to improve the throughput of variant interpretation and to improve understanding of variation in diverse populations as it relates to interpreting genetic test results.  Lastly, ClinGen will disseminate the collective knowledge and resources for unrestricted use in the community and for use in EHR ecosystems.

Goals of ClinGen
  • Share genomic and phenotypic data through centralized databases for clinical and research use.
  • Standardize clinical annotation and interpretation of variants.
  • Improve understanding of variation in diverse populations.
  • Develop machine-learning algorithms to improve the throughput of variant interpretation.
  • Implement evidence-based expert consensus for curation of clinical validity.
  • Assess the 'medical actionability' of genes and variants to support their use in clinical care systems
  • Disseminate the collective knowledge/resources and ensure EHR interoperability.

Top of page

ClinGen Principal Investigators and Their Roles in the ClinGen Consortium

 The following groups are receiving grants:
  • Heidi L. Rehm, Ph.D., Brigham and Women's Hospital, Boston; David H. Ledbetter, Ph.D., and Christa L. Martin, Ph.D., Geisinger Health System, Danville, Pa.; 

    This group is developing standard formats for gathering and depositing data into ClinVar. It will work with clinical laboratories and with specific gene databases to facilitate their submissions to ClinVar and to reduce discrepancies in variant classification.  They have also created GenomeConnect, a patient registry, to help people share de-identified genetic and health information with researchers and connect them with other patients.
     
  • Jonathan S. Berg, M.D., Ph.D, and James P. Evans, M.D., Ph.D, University of North Carolina, Chapel Hill
    David H. Ledbetter, Ph.D., Geisinger Health System, Danville, Pa.
    Michael S. Watson, Ph.D., American College of Medical Genetics and Genomics, Bethesda, Md.


    This group is defining categories of clinical relevance and medical actionability for genes and variants. They have organized clinical domain working groups with experts in hereditary (germline) cancer, somatic cancer, cardiovascular disease, inborn errors of metabolism, and pharmacogenomics to focus on evaluating variants for clinical relevance.  Lastly, they are exploring ways to integrate this information into electronic health records.
     
  • Carlos D. Bustamante, Ph.D., Stanford University, Palo Alto, Calif.
    Sharon E. Plon, M.D., Ph.D., Baylor College of Medicine, Houston


    This group is working closely with the other grants to develop a robust curation system to analyze the clinical validity of gene-disease associations and to implement the ACMG guidelines for interpreting sequencing variants.  The team is developing the ClinGen Knowledge Base (ClinGenKB) and investigating the feasibility of a controlled-access case-level genetic repository.

Top of page

ClinGen Working Groups

 

Working Group Chairs Description Contact
Genomic Variation


Christa Martin, Sharon Plon, & Heidi Rehm
 

Develop variant classification and curation standards and facilitate the submission of sequence and structural variants to ClinVar Danielle Azzariti
(dazzariti@partners.org
& Erin Riggs
(eriggs@geisinger.edu)
 
Phenotyping
David Miller
 
Develops approaches for the standardization and enhanced collection of phenotypic data for annotating genetic variants
Juliann Koenig
(jkoenig@geisinger.edu)
 
Data Modeling Larry Babb
Provide a common set of definitions and consistent representation of core concepts, attributes and terminology to support ClinGen and harmonize with relevant standards efforts.
and terminology, and consistency
 
Danielle Azzariti
(dazzariti@partners.org)
Informatics and Analysis Carlos Bustamante
Coordinate the acquisition, analysis, and
dissemination of ClinGen resource data
Cody Sam
(codysam@stanford.edu)
 
Gene Curation Jonathan Berg &
Christa Martin
 

Develop evidence-based methods for evaluating gene-disease associations to support gene curation activities across
the ClinGen project
 

Laura Milko & Erin Riggs (laura_milko@med.unc.edu & eriggs@geisinger.edu)
 
Actionability Jim Evans &
Katrina Goddard

 

Identify those human genes that, when significantly altered,
confer a high risk of serious disease that could be prevented or mitigated if the risk were known
 

Kristy Lee
(kristy_lee@med.unc.edu)
Somatic Cancer Clinical Domain WG Subha Madhavan, Shashi Kulkarni Coming Soon
Meredith Weaver
(mweaver@ACMG.NET)

 
Hereditary (Germline) Cancer Clinical Domain WG Matthew Ferber, Ken Offit, Sharon Plon Centralize and curate genetic knowledge in order to develop guidance for molecular diagnostic germline cancer testing Kristy Lee
(kristy_lee@med.unc.edu)
Cardio-vascular Disease Clinical Domain WG Euan Ashley, Birgit Funke, Ray Hershberger Create a comprehensive, standardized knowledge base of genes and variants relevant for cardiovascular genetic and genomic medicine Laura Milko
(laura_milko@med.unc.edu)
Inborn Errors of Metabolism Clinical Domain WG Rong Mao, Robert Steiner, William Craigen Create a comprehensive, standardized knowledge base of genes and variants relevant for metabolic diseases and genomic medicine Meredith Weaver
(mweaver@ACMG.NET)
Pharmaco-genomics Clinical Domain WG Teri Klein, Howard McLeod Integrate knowledge about human genetic variation
to inform drug response

Andy Rivera
(andy_rivera@MED.UNC.EDU

Education, Engagement and Counseling Andy Faucett,
Erin Riggs
 
Foster community engagement in all aspects of the ClinGen project through education, outreach, and resource development Erin Riggs
(eriggs@geisinger.edu)
 
Consent and Disclosures Recommendations Committee (CADRe)
Andy Faucett &
Kelly Ormond
 

Explore the ethical, legal, and social (ELSI) issues relating to reporting the actionability of particular genes/variants
in the clinical care process
 
Miranda Hallquist (mhallquist@geisinger.edu)
EHR Integration Marc Williams
Ensure that the ClinGen resource is designed to be accessible to providers and patients through
electronic health record and related systems
 

Meredith Weaver
(mweaver@ACMG.NET)
 

 

Chart with ClinGen database, clinical labs, ClinVar, diseases and other resources

 

Patients, clinicians, labs, researchers sharing genetic and health data - Clingen's critical questions - Is this gene associated with a disease? Is this variant causative? Is this information actionable? - Building a genomic knowledge base - Improved patient care through genomic medicine

Top of page

External Scientific Panel

  • Rex Chisholm, Northwestern University - Chair
  • Debra Leonard, University of Vermont
  •  John Carpten, Translational Genomics Research Institute
  • Olufunmailayo Olopade, University of Chicago
  • Holly Peay, Parent Project Muscular Dystrophy
  • Peter Tarczy-Hornoch, University of Washington
  • Richard Sharp, Cleveland Clinic

Top of page

Funding Announcements and Press Releases

 
RFA-HG-12-016: [grants.nih.gov] Clinically Relevant Genetic Variants Resource: A unified Approach for Identifying Genetic Variants for Clinical Use (U01) 
Press Release: New NIH-funded resource focuses on use of genomic variants in medical care (September 25, 2013)

Top of page

Resources

Websites
ClinGen Website: http://clinicalgenome.org/ 
ClinAction Workshop:  http://www.genome.gov/27546546/ClinAction-Agenda-PowerPoints-and-Videos
ClinVar: http://www.ncbi.nlm.nih.gov/clinvar/
GenomeConnect: http://clinicalgenome.org/genomeconnect/for-participants/
 
Papers

Kirkpatrick, B. E., Riggs, E. R., Azzariti, D. R., Miller, V. R., Ledbetter, D. H., Miller, D. T., ... & Faucett, W. A. GenomeConnect: Matchmaking Between Patients, Clinical Laboratories, and Researchers to Improve Genomic Knowledge. Human mutation36(10), 974-978. 2015. [PubMed]

Ramos EM, Din-Lovinescu C, Berg JS, et al., Characterizing Genetic Variants for Clinical Action. American Journal of Medical Genetics Part C: Seminars in Medical Genetics (special issue on implementation of genomic medicine), 166, No. 1, pp. 93-104. 2014. [PubMed]

Rehm, H. L., Berg, J. S., Brooks, L. D., Bustamante, C. D., Evans, J. P., Landrum, M. J., ... & Watson, M. S. ClinGen-The Clinical Genome Resource. New England Journal of Medicine. 2015. [PubMed]

Top of page

Contacts

Program Directors

Erin Ramos, Ph.D., M.P.H.
Lisa Brooks, Ph.D.
Carolyn Hutter, Ph.D.
Dave Kaufman, Ph.D.

Program Analysts

Annie Niehaus, NHGRI
Kira Wong  

Other IC Funding

Danuta Krotoski, NICHD
Andy Freedman, NCI
Kelly Filipski, NCI

Top of page

Last Updated: October 2, 2015