How I curate: applying American Society of Hematology-Clinical Genome Resource Myeloid Malignancy Variant Curation Expert Panel rules for RUNX1 variant curation for germline predisposition to myeloid malignancies
David Wu,
Xi Luo,
Simone Feurstein,
Chimene Kesserwan,
Shruthi Mohan,
Daniel E. Pineda-Alvarez,
Lucy A. Godley,
on behalf of the collaborative group of the American Society of Hematology - Clinical Genome Resource Myeloid Malignancy Variant Curation Expert Panel
Affiliations
David Wu
Department of Laboratory Medicine, University of Washington, Seattle, WA
Xi Luo
Department of Pediatrics/Hematology-Oncology, Baylor College of Medicine, Houston, TX
Simone Feurstein
Section of Hematology/Oncology, Department of Medicine, and The University of Chicago Comprehensive Cancer Center, Chicago, IL
Chimene Kesserwan
Albert Einstein College of Medicine, Department of Pathology, New York, NY
Shruthi Mohan
Department of Genetics, University of North Carolina School of Medicine, Chapel Hill, NC
Daniel E. Pineda-Alvarez
Invitae, San Francisco, CA
Lucy A. Godley
Section of Hematology/Oncology, Department of Medicine, and The University of Chicago Comprehensive Cancer Center, Chicago, IL;Department of Human Genetics, The University of Chicago, Chicago, IL, USA
on behalf of the collaborative group of the American Society of Hematology - Clinical Genome Resource Myeloid Malignancy Variant Curation Expert Panel
The broad use of next-generation sequencing and microarray platforms in research and clinical laboratories has led to an increasing appreciation of the role of germline mutations in genes involved in hematopoiesis and lineage differentiation that contribute to myeloid neoplasms. Despite implementation of the American College of Medical Genetics and Genomics and Association for Molecular Pathology 2015 guidelines for sequence variant interpretation, the number of variants deposited in ClinVar, a genomic repository of genotype and phenotype data, and classified as having uncertain significance or being discordantly classified among clinical laboratories remains elevated and contributes to indeterminate or inconsistent patient care. In 2018, the American Society of Hematology and the Clinical Genome Resource co-sponsored the Myeloid Malignancy Variant Curation Expert Panel to develop rules for classifying gene variants associated with germline predisposition to myeloid neoplasia. Herein, we demonstrate application of our rules developed for the RUNX1 gene to variants in six examples to show how we would classify them within the proposed framework.
