THE ATLAS OF VARIANT EFFECTS ALLIANCE

Poster presented at the 2024 IGVF Annual Meeting September 24th, 2024 in Seattle, Washington USA DOI: 10.5281/zenodo.13849720 AVE Alliance: https://ror.org/00p2ftz29 https://www.varianteffect.org Abstract: THE ATLAS OF VARIANT EFFECTS ALLIANCE – Advancing Functional Genomics by Engaging the Global Community The Variant Effects Program at the Brotman Baty Institute for Precision Medicine and the University of Washington Department of Genome Sciences aims to develop and deploy multiplexed assays of variant effect (MAVE) to interpret the landscape of human genetic variation to resolve variants of uncertain significance (VUS). Technology development - The Center for the Multiplex Assessment of Phenotype, a Center of Excellence in Genome Science (CEGS) is focused on developing novel technologies for mapping variant effects at scale across a wide range of environmental conditions, genetic contexts, and in multicellular model systems. Data production - Our IGVF characterization centers; the Center for Actionable Variant Analysis (CAVA) and the Shendure/Ahituv/Kircher group, generate functional data at scale for variants in the coding and regulatory sequences of clinically relevant genes. Data standards and federation - We developed MaveDB, the database of record for MAVE-generated data. In collaboration with GA4GH we are developing a shared data model and minimal information standards for functional data. Further, we are collaborating with ClinVar to distribute variant effect data translated for clinical uptake. Community organization - We launched the Atlas of Variant Effects (AVE) Alliance in 2020 to organize the MAVE community. This international community of over 600 researchers, analysts, clinicians, patients and funders from over 40 countries, hail from over 250 institutions. AVE works with and alongside major genomics and genetics initiatives, including NHGRI consortia; CEGS, IGVF, ClinGen and GREGoR. Here we describe the AVE Alliance community outreach efforts, such as the Variant Effects Seminar Series and the Mutational Scanning Symposium, as well as cross-consortium collaborations which align with NHGRIs strategic mission to solve the VUS problem for genomic medicine. Graphics credits: Alex Cagan, Sayeh Gorjifard