103. Defining the pleiotropic GATA2 deficiency phenotype for the development of ACMG-AMP GATA2 variant curation rules

Aly Abdelkareem

Taylor Walker

With every biotechnology innovation, the future of medicine becomes brighter. I hope to be at the forefront of discovery through research, drawing on my interdisciplinary background to approach issues from a new perspective.

Through both my research and my lived experiences, I have seen firsthand how access to health resources can dramatically impact one’s well-being, and I am inspired to make an impact. Previously, I studied cell and tissue engineering, as well as drug delivery, while also researching the human microbiome as an opportunity for health intervention at Cornell University. Currently, I draw upon my tissue engineering background to research myeloid leukemias.

Outside my work, I enjoy video games, fantasy novels, creative writing, learning new skills, and traveling to the most beautiful places on earth. I am excited to get into my career, and I can’t wait to see what the future holds for medicine!


Taylor Walkera, Shruthi Mohanb, Eran Tallisc, Sioban Keeld, Marcin Wlodarskie, Amy Hsuf, Katherine Calvof, Simone Feursteing, Panagiotis Baliakash, Xi Luoi, Guimin Gaoj, David Wud, Lucy Godleyj

aUniversity of Chicago ’21-23, Northwestern University ’23, Country Club Hills, IL, United States; bUniversity of North Carolina, Chapel Hill, NC, United States; cUniversity of Rochester Medical Center, Rochester, NY, United States; dUniversity of Washington, Seattle, WA, United States; eSt. Jude, Memphis, TN, United States; fNIH, Bethesda, MD, United States; gHeidelberg University Hospital, Heidelberg, Germany; hUppsala University Hospital, Uppsala, Sweden; iBaylor College of Medicine, Houston, TX, United States; jUniversity of Chicago, Chicago, IL, United States

The ClinGen Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) focuses on the development of curation rules for variants in several genes that confer risk for myeloid malignancies, such as GATA2. The absence of a defined GATA2 deficient phenotype description challenges the direct application of disease-related ACMG-AMP codes. Therefore, the MM-VCEP is drafting a consensus definition of the GATA2 deficiency based on the phenotypic presentation of individuals from multiple centers worldwide using a modified Delphi approach. A detailed questionnaire including to collect phenotypic data on individuals with deleterious germline GATA2 variants. Individual phenotype data were collected on 110 phenotypes previously attributed to GATA2 deficiency from 437 individuals (340 individuals with confirmed germline variants, and 97 with suspected germline variants) from 17 centers across seven countries, representing the largest patient cohort ever assembled. The most frequently reported phenotypes were pancytopenia (36%), myelodysplastic syndrome (MDS, 59%), and human papilloma virus (HPV)-related warts (53%), with some variation in frequencies by age. These frequencies will be compared to those seen in normal populations, with the UKBiobank serving as the comparator for those over 40 years old. The MM-VCEP plans to develop a weighted scoring system of clinical and laboratory parameters that will define GATA2 deficiency phenotype, and with this consensus phenotype description, the MM-VCEP will complete its GATA2 variant curation rules