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
Open Access
- 12 March 2020
- journal article
- review article
- Published by Ferrata Storti Foundation (Haematologica) in Haematologica
- Vol. 105 (4), 870-887
- https://doi.org/10.3324/haematol.2018.214221
Abstract
The broad use of next-generation sequencing and microarray platforms in the research and clinical laboratories has led to an increasing appreciation for the role of germline mutations in genes involved in hematopoiesis and lineage differentiation in contributing 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 6 examples to show how we would classify them within the proposed framework.This publication has 79 references indexed in Scilit:
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