Recommendations for clinical interpretation of variants found in non-coding regions of the genome.
Full text not available from this repository.Item Type: | Article |
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Official URL: | https://doi.org/10.1186/s13073-022-01073-3 |
Journal or Publication Title: | Genome Medicine |
Volume: | 14 |
Number: | 1 |
Date: | 19 July 2022 |
Divisions: | Bioinformatics and Molecular Genetics Molecular Cardiology |
Depositing User: | General Admin |
Identification Number: | 10.1186/s13073-022-01073-3 |
ISSN: | 1756-994X |
Date Deposited: | 08 Jan 2023 23:11 |
Abstract: | Background: The majority of clinical genetic testing focuses almost exclusively on regions of the genome that directly encode proteins. The important role of variants in non-coding regions in penetrant disease is, however, increasingly being demonstrated, and the use of whole genome sequencing in clinical diagnostic settings is rising across a large range of genetic disorders. Despite this, there is no existing guidance on how current guidelines designed primarily for variants in protein-coding regions should be adapted for variants identified in other genomic contexts. Methods: We convened a panel of nine clinical and research scientists with wide-ranging expertise in clinical variant interpretation, with specific experience in variants within non-coding regions. This panel discussed and refined an initial draft of the guidelines which were then extensively tested and reviewed by external groups. Results: We discuss considerations specifically for variants in non-coding regions of the genome. We outline how to define candidate regulatory elements, highlight examples of mechanisms through which non-coding region variants can lead to penetrant monogenic disease, and outline how existing guidelines can be adapted for the interpretation of these variants. Conclusions: These recommendations aim to increase the number and range of non-coding region variants that can be clinically interpreted, which, together with a compatible phenotype, can lead to new diagnoses and catalyse the discovery of novel disease mechanisms. Keywords: Gene regulation; Non-coding variation; Variant interpretation. |
Creators: | Creators Email Ellingford, Jamie M. UNSPECIFIED Ahn, Joo Wook UNSPECIFIED Bagnall, Richard D. UNSPECIFIED Baralle, Diana UNSPECIFIED Barton, Stephanie UNSPECIFIED Campbell, Chris UNSPECIFIED Downes, Kate UNSPECIFIED Ellard, Sian UNSPECIFIED Duff-Farrier, Celia UNSPECIFIED FitzPatrick, David R. UNSPECIFIED Greally, John M. UNSPECIFIED Ingles, Jodie UNSPECIFIED Krishnan, Neesha UNSPECIFIED Lord, Jenny UNSPECIFIED Martin, Hilary C. UNSPECIFIED Newman, William G. UNSPECIFIED O’Donnell-Luria, Anne UNSPECIFIED Ramsden, Simon C. UNSPECIFIED Rehm, Heidi L. UNSPECIFIED Richardson, Ebony UNSPECIFIED Singer-Berk, Moriel UNSPECIFIED Taylor, Jenny C. UNSPECIFIED Williams, Maggie UNSPECIFIED Wood, Jordan C. UNSPECIFIED Wright, Caroline F. UNSPECIFIED Harrison, Steven M. UNSPECIFIED Whiffin, Nicola UNSPECIFIED |
Last Modified: | 08 Jan 2023 23:11 |
URI: | https://eprints.centenary.org.au/id/eprint/1344 |
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