Human Mutation Special Issue Features ClinGen, a GA4GH Driver Project

October 12th 2018

In a 25-paper special issue of the journal Human Mutation, members of the Clinical Genome Resource (ClinGen) discuss how it is advancing knowledge on the genetic precursors to disease. ClinGen provides a platform for research and clinical experts to review genetic variants that have been associated with disease and determine whether they are actually pathogenic. These expert classifications are submitted to ClinVar, an NIH-hosted database of variant information which clinicians draw from to diagnose and treat patients and which researchers use to guide their studies.

One of the papers in the special issue, “ClinGen Advancing Genomic Data-Sharing Standards as a GA4GH Driver Project,” is co-authored by members of both the ClinGen and GA4GH communities and highlights the ways in which ClinGen, as a GA4GH Driver Project, is contributing to standards development underway in the GA4GH Work Streams.

In particular, ClinGen is deeply involved with the GA4GH Genomic Knowledge Standards (GKS), Clinical and Phenotypic Data Capture (CPDC), and Discovery Work Streams. Through these interactions, the group is helping to develop (i) a standard model for computer readable variant representation, (ii) a data model for linking variant data to annotations, (iii) a network for sharing knowledge about genomic variants and associated clinical interpretations, and (iv) recommended phenotype & disease ontologies and best practices for their use in genomic medicine.

Genomic variants are described with many naming conventions, making it difficult to unambiguously define a variant and ensure the accurate use of associated knowledge. GKS seeks to harmonise this information, and is drawing significantly on prior work from ClinGen’s Data Modeling Work Group, as well as other organizations. The ClinGen Allele Registry plans to define a pilot project to implement the GKS Variant Representation specification, which is currently available in a beta version and proposes a language and nomenclature for describing variation. GKS is also developing a common data model to guide how variant evidence is linked to clinical information with a standard format, based in part on use cases and preliminary work done within ClinGen.

With input from GKS and CPDC, the Discovery Work Stream is developing standards for sharing variant classifications and supporting evidence such as that contained in ClinVar. The standards developed in this effort will be foundational for ClinGen’s knowledge bases. In addition, ClinGen is also implementing the standard phenotype and disease ontologies and best practices, and methods for exchanging such information, being developed within CPDC.

These efforts represent the most recent iteration of a long history of collaboration between ClinGen and GA4GH. Together the two groups developed guidelines for sharing pediatric genomic data and variant-level information in ClinVar, as well as consent resources for clinical genomic data sharing. ClinGen has also been a key contributor to the BRCA Challenge, one of GA4GH’s four early demonstration projects.

“The close partnership between ClinGen and GA4GH illustrates how clinical research consortia can be leveraged to contribute significantly to even larger initiatives,” said Robert Freimuth, an Assistant Professor of Medical Informatics at the Mayo Clinic, co-lead of the GA4GH GKS Work Stream, and a member of the ClinGen Data Exchange and EHR Working Groups. “The success of this collaboration is a model for the development of the shared resources that are imperative for the scalable implementation of clinical genomics.”

Read more about the full issue in the NIH press release.


ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.

The Global Alliance for Genomics and Health (GA4GH) is an international, nonprofit alliance formed in 2013 to accelerate the potential of research and medicine to advance human health. Bringing together 500+ leading organizations working in healthcare, research, patient advocacy, life science, and information technology, the GA4GH community is working together to create frameworks and standards to enable the responsible, voluntary, and secure sharing of genomic and health-related data. All of GA4GH builds upon the Framework for Responsible Sharing of Genomic and Health-Related Data.