On May 27, 2020, an analyses of the largest publicly available catalog of human genomic data revealed new details on rare types of genetic variation and provide better tools for genetic disease diagnosis and drug development. The Genome Aggregation Database (gnomAD) Consortium (and its predecessor, the Exome Aggregation Consortium, or ExAC) compiled and studied more than 125,000 exomes and 15,000 whole genomes from populations around the world.

In seven papers published in Nature, Nature Communications, and Nature Medicine, gnomAD Consortium scientists describe their first set of discoveries from the database, showing the power of this vast collection of data. Together the studies:

1. present a more complete catalog and understanding of a class of rare genetic variation called loss-of-function (LoF) variants, which are thought to disrupt genes’ encoded proteins;
2. introduce the largest comprehensive reference map of an understudied yet important class of genetic variation called structural variants; 
3. show how tools that account for unique forms of variation and variants’ biological context can help clinical geneticists when trying to diagnose patients with rare genetic disease; and
4. illustrate how population-scale datasets like gnomAD can help evaluate proposed drug targets.

Researchers at the Broad Institute of MIT and Harvard and Massachusetts General Hospital (MGH) served as co-first or co-senior authors on all of the studies, with scientists from Imperial College London in the United Kingdom, the direct-to-consumer genetics company 23andMe, and other institutions contributing to individual papers. More than 100 scientists and groups internationally have provided data and/or analytical effort to the consortium.