Study findings deliver more certainty for genetic testing diagnoses

3 August 2023

An international study co-led by QIMR Berghofer researchers aims to enhance the accuracy of medical diagnostics based on genetic tests by improving the way the test results are analysed.

The research has been published in the prestigious journal The American Journal of Human Genetics.

Genetic testing helps to identify whether genetic variations in a patient’s DNA could increase their risk of a disease or whether those changes are benign and unlikely to cause harm. This helps doctors to decide on the best treatments or preventative therapies, and is used for investigating inherited diseases, including familial cancers.

As the cost of the genomic sequencing technology becomes cheaper and knowledge grows about genes, clinical testing to identify genetic variants of concern continues to expand rapidly. However, inconsistency in the interpretation of the clinical relevance of variants remains a challenge.

Senior co-author Professor Amanda Spurdle from QIMR Berghofer said the new study is part of an ongoing international effort to ensure clinical classification of genetic variants is standardised around the world.

“Uncertainty about whether a genetic variation in a patient’s DNA could increase their risk of disease creates anxiety. We want to reduce this uncertainty for patients, and clinical personnel who interact with patients.

Professor Amanda Spurdle

“Frameworks around diagnosing genetic variants were designed in 2015, but it’s clear that the application of these guidelines can vary between laboratories around the world, so protocols to standardise guidance are needed.

“Our study provides recommendations to help diagnostic laboratories assess genetic variants, specifically focusing on the aspects related to use of RNA-based lab investigations or computational prediction methods. We came up with detailed guidance on how to review and apply different evidence criteria. This includes evidence-based recommendations on extended use of predictions, to enable more variants to be classified in the future using the existing generic framework.

“We believe this will improve rates of diagnosis for patients, and could pave the way for earlier treatment intervention and predictive testing to help prevent diseases developing,” Professor Spurdle said.

The field of research that was a focus of this study is RNA diagnostics.

DNA contains the inherited genetic information for our bodies, while RNA copies and translates that information to make the proteins that are essential for the body to function.

Studying if and how an RNA molecule is altered by a DNA genetic variant, during a process known as RNA ‘splicing’, can help scientists work out if that variant is of clinical relevance.

Alongside the researchers from QIMR Berghofer, the project involved collaboration with experts from the University of Otago in New Zealand, as well as scientists from the United States and Spain. The team analysed large datasets of genetic testing information from around the world to develop the recommendations.

The researchers undertook the project to provide advice to the Clinical Genome (ClinGen) Resource, funded by the US National Institutes of Health (NIH), which is building a central global resource of information about genes and variants of uncertain significance to help improve patient care.

The study has been published in The American Journal of Genetics and can be accessed at this link


Bridie Barry
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