Global Globin Network and adopting genomic variant database requirements for thalassemia

\ua9 The Author(s) 2024. Published by Oxford University Press.Thalassemia is one of the most prevalent monogenic disorders in low- and middle-income countries (LMICs). There are an estimated 270 million carriers of hemoglobinopathies (abnormal hemoglobins and/or thalassemia) worldwide, necessitating global methods and solutions for effective and optimal therapy. LMICs are disproportionately impacted by thalassemia, and due to disparities in genomics awareness and diagnostic resources, certain LMICs lag behind high-income countries (HICs). This spurred the establishment of the Global Globin Network (GGN) in 2015 at UNESCO, Paris, as a project-wide endeavor within the Human Variome Project (HVP). Primarily aimed at enhancing thalassemia clinical services, research, and genomic diagnostic capabilities with a focus on LMIC needs, GGN aims to foster data collection in a shared database by all affected nations, thus improving data sharing and thalassemia management. In this paper, we propose a minimum requirement for establishing a genomic database in thalassemia based on the HVP database guidelines. We suggest using an existing platform recommended by HVP, the Leiden Open Variation Database (LOVD) (https://www.lovd.nl/). Adoption of our proposed criteria will assist in improving or supplementing the existing databases, allowing for better-quality services for individuals with thalassemia. Database URL: https://www.lovd.nl/

Adapting the ACMG/AMP variant classification framework: a perspective from the ClinGen Hemoglobinopathy Variant Curation Expert Panel

Accurate and consistent interpretation of sequence variants is integral to the delivery of safe and reliable diagnostic genetic services. To standardize the interpretation process, in 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published a joint guideline based on a set of shared standards for the classification of variants in Mendelian diseases. The generality of these standards and their subjective interpretation between laboratories has prompted efforts to reduce discordance of variant classifications, with a focus on the expert specification of the ACMG/AMP guidelines for individual genes or diseases. Herein, we describe our experience as a ClinGen Variant Curation Expert Panel to adapt the ACMG/AMP criteria for the classification of variants in three globin genes (HBB, HBA2, and HBA1) related to recessively inherited hemoglobinopathies, including five evidence categories, as use cases demonstrating the process of specification and the underlying rationale.Genetics of disease, diagnosis and treatmen

Harmonizing the interpretation of genetic variants across the world: the Malaysian experience.

BACKGROUND: Databases for gene variants are very useful for sharing genetic data and to facilitate the understanding of the genetic basis of diseases. This report summarises the issues surrounding the development of the Malaysian Human Variome Project Country Node. The focus is on human germline variants. Somatic variants, mitochondrial variants and other types of genetic variation have corresponding databases which are not covered here, as they have specific issues that do not necessarily apply to germline variations. RESULTS: The ethical, legal, social issues, intellectual property, ownership of the data, information technology implementation, and efforts to improve the standards and systems used in data sharing are discussed. CONCLUSION: An overarching framework such as provided by the Human Variome Project to co-ordinate activities is invaluable. Country Nodes, such as MyHVP, enable human gene variation associated with human diseases to be collected, stored and shared by all disciplines (clinicians, molecular biologists, pathologists, bioinformaticians) for a consistent interpretation of genetic variants locally and across the world