From Expert Judgment to Structured Guidelines: A Brief History and Bright Future of DNA Variant Interpretation

被引：0

作者：

Laner, Andreas ^{[1
]}

Zilfalil, Bin Alwi ^{[2
]}

Hamed, Sherifa Ahmed ^{[3
]}

Do, Huy ^{[4
]}

Lopes-Cendes, Iscia ^{[5
]}

Shrestha, Tilak ^{[6
]}

Tobias, Edward ^{[7
]}

Solano, Angela ^{[8
]}

Hamosh, Ada ^{[9
]}

Kumar, Dhavendra ^{[10
]}

机构：

[1] Med Genet Zentrum MGZ, Munich, Germany

[2] Univ Sains Malaysia, Sch Med Sci, Human Genome Ctr, Kelantan, Malaysia

[3] Assiut Univ, Fac Med, Dept Neurol & Psychiat, Assiut, Egypt

[4] Vietnamese Org Rare Dis VORD, Ho Chi Minh City, Vietnam

[5] Univ Estadual Campinas, Sch Med Sci, Dept Med Genet & Genom Med, Campinas, SP, Brazil

[6] Tribhuvan Univ, Cent Dept Biotechnol, Kathmandu, Nepal

[7] Univ Glasgow, Queen Elizabeth Univ Hosp, West Scotland Ctr Genom Med, Glasgow, Scotland

[8] CABA, Dept Clin Chem, Ctr Educ Med Invest Clin Dr Norberto Quirno, Lab Genotyping, Buenos Aires, Argentina

[9] Johns Hopkins Univ, Sch Med, McKusick Nathans Dept Genet Med, Baltimore, MD USA

[10] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England

来源：

ANNALS OF HUMAN GENETICS | 2025年

关键词：

ACMG/AMP classification system; ClinGen; HUGO Education Committee; variant interpretation; variant of uncertain significance; JOINT CONSENSUS RECOMMENDATION; GENETIC-VARIANTS; ACMG RECOMMENDATIONS; SEQUENCE VARIANTS; MEDICAL GENETICS; AMERICAN-COLLEGE; BRCA2; VARIANTS; CLASSIFICATION; STANDARDS; IDENTIFICATION;

D O I：

10.1111/ahg.70009

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

BackgroundThe classification of sequence variants is at the core of human genetic diagnostics and is the basis for clinical guidance - incorrectly classified variants may cause great harm to patients and their families.MethodsWe provide an overview of the evolution of ideas and algorithms that have led to the formulation of elaborate classification systems over the last decades, culminating in the ACMG/AMP classification system. Furthermore, we address a still unsolved problem in the clinical translation of DNA analyses: variants of unclear significance (VUS).ResultsRigorous data sharing and the sub-categorisation of VUS could facilitate a clearer interpretation of VUS.ConclusionThis review underscores the efforts of the HUGO Education Committee to empower professional-sespecially in resource-limited settings-with the expertise needed for high-quality variant interpretation, fostering equitable access to the transformative potential of genomic medicine.

引用

页数：12

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