Haematologica (Apr 2020)

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

DOI
https://doi.org/10.3324/haematol.2018.214221
Journal volume & issue
Vol. 105, no. 4

Abstract

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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.