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Pathology Update 2025
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Recommendations for classification of variants in non-coding regions

Scientific Program
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Scientific Program

11:00 am

22 February 2025

Meeting Room 109

Scientific Session - Genetic - Variant Classification

Discipline Streams

Genetic Pathology

Abstracts/Presentation Description

Nicola Whiffin1
1University of Oxford

The globally adopted American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP) guidelines for variant interpretation were primarily designed for protein coding variants.

We convened a panel of clinical and research scientists with wide-ranging expertise in clinical variant interpretation, with specific experience in variants within non-coding regions. Our aim was to design a set of recommendations, intended to sit alongside the existing ACMG/AMP guidelines, outlining specific considerations and adaptations relevant to variants across the range of non-coding regions. The guidelines were extensively tested on a set of 30 variants across a range of non-coding regions. This exercise highlighted a number of barriers to use of the guidelines in a diagnostic setting.

Our recommendations aim to increase the number and range of non-coding region variants that can be interpreted clinically. We anticipate that this will lead to an increase in new diagnosis for rare disease patients and catalyse the discovery of novel disease mechanisms.

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