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From Expert Judgment to Structured Guidelines: A Brief History and Bright Future of DNA Variant Interpretation
Andreas Laner1, Bin Alwi Zilfalil2, Sherifa Ahmed Hamed3
1Medizinisch Genetisches Zentrum (MGZ), Munich, Germany.
Annals of Human Genetics
|July 15, 2025
Summary
Accurate human genetic variant classification is crucial for patient care. Sharing data and sub-categorizing variants of unclear significance (VUS) can improve interpretation and genomic medicine accessibility.
Area of Science:
- Genetics
- Clinical Diagnostics
- Bioinformatics
Background:
- Accurate classification of human genetic variants is essential for clinical diagnostics and patient guidance.
- Misclassification of variants can lead to significant harm for patients and their families.
Purpose of the Study:
- To review the evolution of variant classification systems, including the ACMG/AMP system.
- To address the challenge of interpreting variants of unclear significance (VUS) in clinical DNA analyses.
Main Methods:
- Historical overview of classification algorithms and systems.
- Discussion of challenges in clinical translation of DNA analysis.
- Exploration of solutions for VUS interpretation.
Main Results:
- Rigorous data sharing is proposed as a method to improve variant interpretation.
- Sub-categorization of VUS is identified as a strategy to enhance clarity.
Conclusions:
- Efforts are underway to empower professionals, especially in resource-limited settings, with variant interpretation expertise.
- Fostering equitable access to genomic medicine is a key objective.
Keywords:
ACMG/AMP classification systemClinGenHUGO Education Committeevariant interpretationvariant of uncertain significanceMore Related Videos
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