Evidence map›Paper›PMID 37066232›Full record

ArticlemedRxiv : the preprint server for health sciences2023

Towards robust clinical genome interpretation: developing a consistent terminology to characterize disease-gene relationships - allelic requirement, inheritance modes and disease mechanisms.

Angharad M Roberts, Marina T DiStefano, Erin Rooney Riggs, Katherine S Josephs, Fowzan S Alkuraya, Joanna Amberger, Mutaz Amin, Jonathan S Berg, Fiona Cunningham, Karen Eilbeck and 16 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

Angharad M RobertsNational Heart & Lung Institute & MRC London Institute of Medical Sciences, Imperial College London, London, UK.
Marina T DiStefanoMedical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Erin Rooney RiggsGeisinger Autism & Developmental Medicine Institute, Danville, PA, USA.
Katherine S JosephsNational Heart & Lung Institute & MRC London Institute of Medical Sciences, Imperial College London, London, UK.
Fowzan S AlkurayaDepartment of Translational Genomics, Center for Genomic Medicine, KFSHRC, Riyadh, Saudi Arabia.
Joanna AmbergerOnline Mendelian Inheritance in Man (OMIM), Johns Hopkins University School of Medicine, USA.
Mutaz AminINSERM, US14-Orphanet, Paris, France.
Jonathan S BergDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill NC, 27599.
Fiona CunninghamEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SD, United Kingdom.
Karen EilbeckDepartment of Biomedical Informatics, University of Utah, Salt Lake City, Utah.
Helen V FirthDept of Medical Genetics, Cambridge University Hospitals, Cambridge CB2 0QQ, UK.
Julia ForemanWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK.
Ada HamoshOnline Mendelian Inheritance in Man (OMIM), Johns Hopkins University School of Medicine, USA.
Eleanor HayDept of Medical Genetics, Great Ormond Street Hospital, Great Ormond Street, London. WC1N 3JH, UK.
Sarah LeighGenomics England, Queen Mary University of London, Dawson Hall, London, EC1M 6BQ, UK.
Christa L MartinClinical Genome Resource (ClinGen), USA.
Ellen M McDonaghEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SD, United Kingdom.
Daniel PerrettEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SD, United Kingdom.
Erin M RamosNational Human Genome Research Institute, National Institutes of Health, USA.
Peter N RobinsonThe Jackson Laboratory for Genomic Medicine, Farmington CT 06032, USA.
Ana RathINSERM, US14-Orphanet, Paris, France.
David van SantDepartment of Biomedical Informatics, University of Utah, Salt Lake City, Utah.
Zornitza StarkAustralian Genomics, Melbourne 3052, Australia.
Nicola WhiffinMedical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Heidi L RehmMedical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
James S WareNational Heart & Lung Institute & MRC London Institute of Medical Sciences, Imperial College London, London, UK.

Funding

The Clinical Genome Resource – Advancing genomic medicine through biocuration and expert assessment of genes and variants at scaleU24HG009650 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JONATHAN S BERG, Jessica Ezzell Hunter · 2021 to 2026
$30.0M
ClinGen AI Data Delivery SupplementU24HG006834 · NHGRI · BROAD INSTITUTE, INC. · PI Marina DiStefano, CHRISTA LESE MARTIN · 2021 to 2026
$26.7M
UNIVERSITY OF UTAH MEDICAL INFORMATICS TRAININGT15LM007124 · NLM · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Karen Louise Eilbeck · 1997 to 2026
$22.0M
The Human Phenotype Ontology: Accelerating Computational Integration of Clinical Data for GenomicsU24HG011449 · NHGRI · JACKSON LABORATORY · PI Peter Nicholas Robinson · 2021 to 2026
$6.7M
NHGRI NIH HHS U24 HG006834NHGRI NIH HHS U24 HG009650NHGRI NIH HHS U24 HG011449NLM NIH HHS T15 LM007124Wellcome Trust
6 · The paper itself

Abstract

purposeThe terminology used for gene-disease curation and variant annotation to describe inheritance, allelic requirement, and both sequence and functional consequences of a variant is currently not standardized. There is considerable discrepancy in the literature and across clinical variant reporting in the derivation and application of terms. Here we standardize the terminology for the characterization of disease-gene relationships to facilitate harmonized global curation, and to support variant classification within the ACMG/AMP framework.

methodsTerminology for inheritance, allelic requirement, and both structural and functional consequences of a variant used by Gene Curation Coalition (GenCC) members and partner organizations was collated and reviewed. Harmonized terminology with definitions and use examples was created, reviewed, and validated.

resultsWe present a standardized terminology to describe gene-disease relationships, and to support variant annotation. We demonstrate application of the terminology for classification of variation in the ACMG SF 2.0 genes recommended for reporting of secondary findings. Consensus terms were agreed and formalized in both sequence ontology (SO) and human phenotype ontology (HPO) ontologies. GenCC member groups intend to use or map to these terms in their respective resources.

conclusionThe terminology standardization presented here will improve harmonization, facilitate the pooling of curation datasets across international curation efforts and, in turn, improve consistency in variant classification and genetic test interpretation.

Identifiers

PMID37066232
PMCPMC10104222

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