ClinGen: New clinical genome resource may help understand clinical implications of genetic variants

Tremendous advances have been made in decoding the human genome in recent years but critical questions remain regarding what these variants mean and how they can be applied in clinical practice. In a comprehensive paper to be published in The New England Journal of Medicine on May 27, 2015, "ClinGen: The Clinical Genome Resource," a consortium including investigators from the American College of Medical Genetics and Genomics (ACMG) provide a detailed overview of ClinGen, an NIH-supported program to evaluate the clinical relevance of genetic variants for use in precision medicine and to increase the understanding of their role in human health and disease.

ACMG Executive Director Michael S. Watson, PhD, FACMG said, " With ClinGen and ClinVar now in place to manage the big data problem inherent in medical genomics, we are well positioned to enable extensive data sharing among laboratories and clinician. This is expected to dramatically improve our understanding of the clinical implications of genetic variation and its role in improving patient and population health."

ClinGen's mission is to build a genomic knowledgebase to improve patient care. Genetic clinicians and medical researchers hope to use information about genetic variants in a variety of ways including making better predictions about an individual's risk of disease, to developing tailored treatments and to improve clinical decision-making.

"We're dealing with massive amounts of information: more than 80 million genetic variants have been discovered to date, and for most of them, we have no clear understanding of their role in human health and disease," said Heidi Rehm, PhD, associate professor of Pathology at BWH and director of the Laboratory for Molecular Medicine at Partners HealthCare Personalized Medicine and lead author of the paper. As genetic sequencing becomes more common, interpreting data in a meaningful way and standardizing practices is imperative. The enormity of the situation is daunting, but the potential impact on patient care has immense implications."

The paper in NEJM states, "...the American College of Medical Genetics and Genomics (a ClinGen grantee), working with members of the sequence and structural variant communities, have developed new standards for interpreting genetic variants. ClinGen is now working with laboratories to facilitate adoption of the new standards and openly share the basis of their pathogenicity assertions. This allows labs to resolve interpretation differences through expert consensus and applications of these standardized methods which will rapidly improve the use of genetic testing in the clinical setting."

One important part of ClinGen is ClinVar, a publicly-accessible database launched in April 2013 at the National Center for Biotechnology Information (NCBI), which archives information submitted about genetic variants with medical relevance. Clinicians, researchers and patients can look up information on ClinVar to see what is currently known about a genetic variant. According to the paper's authors, "...the ClinVar database is ...being embraced by patients and physicians as a system for sharing up-to-date information on clinically reported genetic variants."

Source: American College of Medical Genetics