ArticleGenome medicine2022
Recommendations for clinical interpretation of variants found in non-coding regions of the genome.
Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 2 of them syntheses that pooled it.
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Who cites it
171 citing papers in PubMed, 2 syntheses or guidelines pooled it, 241 citations in OpenAlex.
- EMQN best practice guidelines for genetic testing in hereditary breast and ovarian cancer.European journal of human genetics : EJHG · 2024Guideline
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- Mechanisms underlying disease-causing variants in promoters and enhancers.Nature genetics · 2026Review
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- The Global Parkinson's Disease Genetics (GP2) Genome Browser.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Incremental yield of genome sequencing after exome sequencing for nonimmune hydrops fetalis spectrum.American journal of obstetrics & gynecology MFM · 2026Article
- Expanding the Genomic Spectrum ofInternational journal of molecular sciences · 2026Article
- Guidance for clinical variant classification in genes for spliceosomal small nuclear RNAs.medRxiv : the preprint server for health sciences · 2026Article
- A Human Pharmacogenomics Approach Provides Insight Into the Pathogenesis and Pathophysiology of Steroid-Induced Ocular Hypertension.Ophthalmology science · 2026Article
- Best practice recommendations for bioinformatics approaches applied to high-throughput sequencing for rare disease and cancer diagnosis within the UK National Health Service.Journal of medical genetics · 2026Article
- Differentially Methylated Regions in Human Rhombic Lip Compartments Are Enriched in Putative Active Enhancers, Human Accelerated Regions, and Medulloblastoma Copy Number Aberrations.Cerebellum (London, England) · 2026Article
- Whole-genome sequencing implicates rare, low-frequency and structural non-coding variation at themedRxiv : the preprint server for health sciences · 2026Article
- Unlocking the Regulatory Genome: Interpreting the Clinical Impact of Noncoding Variants in Genetic Cardiomyopathies.Circulation. Genomic and precision medicine · 2026Review
- Variant-specific RNA testing resolves variants of uncertain significance in exome testing.BMC genomics · 2026Article
- Review
- RNU4ATAC-opathy: Clinical, molecular, and transcriptomic insights from a large cohort.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- HiFi long-read RNA sequencing enhances clinical diagnostics in rare disorders.European journal of human genetics : EJHG · 2026Article
- A comparative survey of functional evidence use in hearing and vision loss genetics.Communications medicine · 2026Article
111 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 14 institutions in 3 countries.
Funding
Abstract
backgroundThe 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.
methodsWe 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.
resultsWe 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.
conclusionsThese 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.