Myeloid Malignancy Variant Curation Expert Panel

Project Summary Germline predisposition to hematopoietic malignancies is more common than previously appreciated and is best understood for the myeloid malignancies. Variants in genes such as RUNX1, DDX41, GATA2, ANKRD26, ETV6, CEBPA, SAMD9/SAMD9L, and TERT/TERC are among those commonly identified in patients. Recognizing the

importance of germline predisposition to myeloid malignancies, all of the recently-updated classification schema include this entity among their diagnostic criteria. The American Society of Hematology and ClinGen first partnered in 2017 to support the Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP), which was

funded subsequently by the NIH U24 mechanism. In its initial funding period, the MM-VCEP has:organized a diverse biocurator network consisting of a Lead Biocurator and 16 biocurators; developed, implemented, and revised RUNX1 variant curation rules that are now in use throughout the world; completed the first international

As a highly motivated and productive group, the MM-VCEP seeks continued support for curation of RUNX1, DDX41, and GATA2 variants and development of curation rules for additional genes that confer risk for myeloid malignancies, including ANKRD26, ETV6, CEBPA, SAMD9/SAMD9L, and TERT/TERC. The MM-VCEP seeks to use segregation codes

at the strongest level possible and will develop novel collaborations with patient/family-focused organizations, including ConnectMyVariant, the RUNX1 Research Program, and Team Telomere, Inc., to do so. Additional variant collections that have deep phenotype and provider contact information, such as the St. Jude Children’s

Research Hospital SAMD9/SAMD9L database and the Clinical Care Consortium for Telomere-Associated Ailment international registry, will be incorporated as well. Thus, the MM-VCEP seeks to continue its important work in providing worldwide standards for consistent variant curation so that patients at risk of developing myeloid

malignancies can receive optimal clinical care and appropriate surveillance strategies for cancer detection and organ dysfunction. GATA2 Phenotype Survey; and developed pilot curation rules for DDX41 and GATA2.