Recommendations for clinical interpretation of variants found in non-coding regions of the genome

A joint NCBI and EMBL-EBI transcript set for clinical genomics and research

(2022) Joannella Morales et al.   NATURE

Detection of aberrant gene expression events in RNA sequencing data

(2021) Vicente A. Yépez et al.   Nature Protocols

Detection of aberrant splicing events in RNA-seq data using FRASER

(2021) Christian Mertes et al.   Nature Communications

CADD-Splice—improving genome-wide variant effect prediction using deep learning-derived splice scores

(2021) Philipp Rentzsch et al.   Genome Medicine

Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms

(2021) Caroline F. Wright et al.   AMERICAN JOURNAL OF HUMAN GENETICS

A gain-of-function single nucleotide variant creates a new promoter which acts as an orientation-dependent enhancer-blocker

(2021) Yavor K. Bozhilov et al.   Nature Communications

Expanding the genotypic spectrum of TXNL4A variants in Burn‐McKeown syndrome

(2021) Katherine A. Wood et al.   CLINICAL GENETICS

100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report

(2021) et al.   NEW ENGLAND JOURNAL OF MEDICINE

Whole Gene Sequencing of CFTR Reveals a High Prevalence of the Intronic Variant c.3874-4522A>G in Cystic Fibrosis

(2020) Deborah J. Morris-Rosendahl et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Mutation spectrum of PRPF31, genotype-phenotype correlation in retinitis pigmentosa, and opportunities for therapy

(2020) Gabrielle Wheway et al.   EXPERIMENTAL EYE RESEARCH

Blood RNA analysis can increase clinical diagnostic rate and resolve variants of uncertain significance

(2020) Htoo A. Wai et al.   GENETICS IN MEDICINE

Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

(2020) Kadir C. Akdemir et al.   NATURE GENETICS

Towards a comprehensive catalogue of validated and target-linked human enhancers

(2020) Molly Gasperini et al.   NATURE REVIEWS GENETICS

Mapping RNA splicing variations in clinically accessible and nonaccessible tissues to facilitate Mendelian disease diagnosis using RNA-seq

(2020) Joseph K. Aicher et al.   GENETICS IN MEDICINE

Alternative mRNA splicing can attenuate the pathogenicity of presumed loss-of-function variants in BRCA2

(2020) Romy L. S. Mesman et al.   GENETICS IN MEDICINE

The mutational constraint spectrum quantified from variation in 141,456 humans

(2020) Konrad J. Karczewski et al.   NATURE

Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals

(2020) Nicola Whiffin et al.   Nature Communications

DYNC2H1 hypomorphic or retina-predominant variants cause nonsyndromic retinal degeneration

(2020) Anjali Vig et al.   GENETICS IN MEDICINE

Expanded encyclopaedias of DNA elements in the human and mouse genomes

(2020) Jill E. Moore et al.   NATURE

Splicing mutations in inherited retinal diseases

(2020) Nicole Weisschuh et al.   PROGRESS IN RETINAL AND EYE RESEARCH

The GTEx Consortium atlas of genetic regulatory effects across human tissues

(2020)   SCIENCE

Predicting Splicing from Primary Sequence with Deep Learning

(2019) Kishore Jaganathan et al.   CELL

Deep-intronic ABCA4 variants explain missing heritability in Stargardt disease and allow correction of splice defects by antisense oligonucleotides

(2019) Riccardo Sangermano et al.   GENETICS IN MEDICINE

ABCA4-associated disease as a model for missing heritability in autosomal recessive disorders: novel noncoding splice, cis-regulatory, structural, and recurrent hypomorphic variants

(2019) Miriam Bauwens et al.   GENETICS IN MEDICINE

Chromatin accessibility and the regulatory epigenome

(2019) Sandy L. Klemm et al.   NATURE REVIEWS GENETICS

NAA10 polyadenylation signal variants cause syndromic microphthalmia

(2019) Jennifer J Johnston et al.   JOURNAL OF MEDICAL GENETICS

Genetic compensation triggered by mutant mRNA degradation

(2019) Mohamed A. El-Brolosy et al.   NATURE

Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP

(2019) Anja Thormann et al.   Nature Communications

Principles of genome folding into topologically associating domains

(2019) Quentin Szabo et al.   Science Advances

Human 5′ UTR design and variant effect prediction from a massively parallel translation assay

(2019) Paul J. Sample et al.   NATURE BIOTECHNOLOGY

Beyond the Exome: The Non-coding Genome and Enhancers in Neurodevelopmental Disorders and Malformations of Cortical Development

(2019) Elena Perenthaler et al.   Frontiers in Cellular Neuroscience

Developmentally regulated Shh expression is robust to TAD perturbations

(2019) Iain Williamson et al.   DEVELOPMENT

Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)

(2019) Erin Rooney Riggs et al.   GENETICS IN MEDICINE

Activity-by-contact model of enhancer–promoter regulation from thousands of CRISPR perturbations

(2019) Charles P. Fulco et al.   NATURE GENETICS

PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels

(2019) Antonio Rueda Martin et al.   NATURE GENETICS

Rare variants in non-coding regulatory regions of the genome that affect gene expression in systemic lupus erythematosus

(2019) Sarah A. Jones et al.   Scientific Reports

Machine Learning Approaches for the Prioritization of Genomic Variants Impacting Pre-mRNA Splicing

(2019) Charlie F Rowlands et al.   Cells

Recommendations for application of the functional evidence PS3/BS3 criterion using the ACMG/AMP sequence variant interpretation framework

(2019) Sarah E. Brnich et al.   Genome Medicine

Recommendations for the collection and use of multiplexed functional data for clinical variant interpretation

(2019) Hannah Gelman et al.   Genome Medicine

Regulatory variants: from detection to predicting impact

(2018) Elena Rojano et al.   BRIEFINGS IN BIOINFORMATICS

Whole genome sequencing provides better diagnostic yield and future value than whole exome sequencing

(2018) John S Mattick et al.   MEDICAL JOURNAL OF AUSTRALIA

A user's guide to the ambiguous word 'epigenetics'

(2018) John M. Greally   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Eukaryotic core promoters and the functional basis of transcription initiation

(2018) Vanja Haberle et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Recommendations for interpreting the loss of function PVS1 ACMG/AMP variant criterion

(2018) Ahmad N. Abou Tayoun et al.   HUMAN MUTATION

The cis-regulatory dynamics of embryonic development at single-cell resolution

(2018) Darren A. Cusanovich et al.   NATURE

De novo mutations in regulatory elements in neurodevelopmental disorders

(2018) Patrick J. Short et al.   NATURE

Modified penetrance of coding variants by cis-regulatory variation contributes to disease risk

(2018) Stephane E. Castel et al.   NATURE GENETICS

Pathogenicity and selective constraint on variation near splice sites

(2018) Jenny Lord et al.   GENOME RESEARCH

Functional characterization and phenotypic spectrum of three recurrent disease-causing deep intronic variants of the CFTR gene

(2018) A. Bergougnoux et al.   Journal of Cystic Fibrosis

Predicting CTCF-mediated chromatin interactions by integrating genomic and epigenomic features

(2018) Yan Kai et al.   Nature Communications

Using high-resolution variant frequencies to empower clinical genome interpretation

(2017) Nicola Whiffin et al.   GENETICS IN MEDICINE

Single-base substitutions in the CHM promoter as a cause of choroideremia

(2017) Alina Radziwon et al.   HUMAN MUTATION

Evolving health care through personal genomics

(2017) Heidi L. Rehm   NATURE REVIEWS GENETICS

Mutations in noncoding regions of GJB1 are a major cause of X-linked CMT

(2017) Pedro J. Tomaselli et al.   NEUROLOGY

ClinVar: improving access to variant interpretations and supporting evidence

(2017) Melissa J Landrum et al.   NUCLEIC ACIDS RESEARCH

Improving genetic diagnosis in Mendelian disease with transcriptome sequencing

(2017) Beryl B. Cummings et al.   Science Translational Medicine

A Whole-Genome Analysis Framework for Effective Identification of Pathogenic Regulatory Variants in Mendelian Disease

(2016) Damian Smedley et al.   AMERICAN JOURNAL OF HUMAN GENETICS

Looking beyond the genes: the role of non-coding variants in human disease

(2016) Malte Spielmann et al.   HUMAN MOLECULAR GENETICS

Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease

(2016) Jamie M. Ellingford et al.   OPHTHALMOLOGY

Comprehensive RNA Analysis of the NF1 Gene in Classically Affected NF1 Affected Individuals Meeting NIH Criteria has High Sensitivity and Mutation Negative Testing is Reassuring in Isolated Cases With Pigmentary Features Only

(2016) D.G. Evans et al.   EBioMedicine

Disruptions of Topological Chromatin Domains Cause Pathogenic Rewiring of Gene-Enhancer Interactions

(2015) Darío G. Lupiáñez et al.   CELL

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology

(2015) Sue Richards et al.   GENETICS IN MEDICINE

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

(2015) Jenny C Taylor et al.   NATURE GENETICS

The Ensembl Regulatory Build

(2015) Daniel R Zerbino et al.   GENOME BIOLOGY

Genome sequencing identifies major causes of severe intellectual disability

(2014) Christian Gilissen et al.   NATURE

Disruption of Autoregulatory Feedback by a Mutation in a Remote, Ultraconserved PAX6 Enhancer Causes Aniridia

(2013) Shipra Bhatia et al.   AMERICAN JOURNAL OF HUMAN GENETICS

DECIPHER: database for the interpretation of phenotype-linked plausibly pathogenic sequence and copy-number variation

(2013) Eugene Bragin et al.   NUCLEIC ACIDS RESEARCH

cis-regulatory mutations are a genetic cause of human limb malformations

(2011) Julia E. VanderMeer et al.   DEVELOPMENTAL DYNAMICS

Role of 5′- and 3′-untranslated regions of mRNAs in human diseases

(2009) Sangeeta Chatterjee et al.   BIOLOGY OF THE CELL