Evidence map›Paper›PMID 35442193›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2022

The Clinical Variant Analysis Tool: Analyzing the evidence supporting reported genomic variation in clinical practice.

Hui-Lin Chin, Nour Gazzaz, Stephanie Huynh, Iulia Handra, Lynn Warnock, Ashley Moller-Hansen, Pierre Boerkoel, Julius O B Jacobsen, Christèle du Souich, Nan Zhang and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Hui-Lin ChinDepartment of Medical Genetics, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada; Provincial Medical Genetics Program, Women's Hospital of British Columbia, Vancouver, British Columbia, Canada; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, Singapore, Singapore.
Nour GazzazDepartment of Medical Genetics, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada; Provincial Medical Genetics Program, Women's Hospital of British Columbia, Vancouver, British Columbia, Canada; Department of Pediatrics, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada; Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Stephanie HuynhDepartment of Medical Genetics, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada; Provincial Medical Genetics Program, Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
Iulia HandraDepartment of Medical Genetics, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada; Provincial Medical Genetics Program, Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
Lynn WarnockProvincial Medical Genetics Program, Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
Ashley Moller-HansenProvincial Medical Genetics Program, Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
Pierre BoerkoelMD Undergraduate Program, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Julius O B JacobsenWilliam Harvey Research Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom.
Christèle du SouichDepartment of Medical Genetics, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
Nan ZhangBreakthrough Genomics, Irvine, CA.
Kent ShefchekOregon Clinical and Translational Science Institute, Oregon Health & Science University, Portland, OR.
Leah M PrenticeProvincial Laboratory Medicine Services, Provincial Health Services Authority, Vancouver, British Columbia, Canada.
Nicole WashingtonHelix, San Mateo, CA.
Melissa HaendelOregon Clinical and Translational Science Institute, Oregon Health & Science University, Portland, OR.
Linlea ArmstrongDepartment of Medical Genetics, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada; Provincial Medical Genetics Program, Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
Lorne ClarkeDepartment of Medical Genetics, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada; Provincial Medical Genetics Program, Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
Wenhui Laura LiBreakthrough Genomics, Irvine, CA.
Damian SmedleyWilliam Harvey Research Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom.
Peter N RobinsonJackson Laboratory for Genomic Medicine, Farmington, CT.
Cornelius F BoerkoelDepartment of Medical Genetics, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada; Provincial Medical Genetics Program, Women's Hospital of British Columbia, Vancouver, British Columbia, Canada. Electronic address: cboerkoel@gmail.com.

Funding

The Monarch Initiative: Linking Diseases to Model Organism ResourcesR24OD011883 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HAENDEL, MELISSA A, MUNGALL, CHRISTOPHER J · 2012 to 2024
$16.0M
Improvements to the LinkML framework to support the Phenomics First open science resourceRM1HG010860 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HAENDEL, MELISSA A, MUNGALL, CHRISTOPHER J · 2020 to 2024
$10.3M
Increasing the Yield and Utility of Pediatric Genomic Medicine with ExomiserR01HD103805 · NICHD · JACKSON LABORATORY · PI Valentina Cipriani, CHRISTOPHER J MUNGALL · 2021 to 2026
$4.3M
NHGRI NIH HHS RM1 HG010860NICHD NIH HHS R01 HD103805NIH HHS R24 OD011883
6 · The paper itself

Abstract

purposeGenomic test results, regardless of laboratory variant classification, require clinical practitioners to judge the applicability of a variant for medical decisions. Teaching and standardizing clinical interpretation of genomic variation calls for a methodology or tool.

methodsTo generate such a tool, we distilled the Clinical Genome Resource framework of causality and the American College of Medical Genetics/Association of Molecular Pathology and Quest Diagnostic Laboratory scoring of variant deleteriousness into the Clinical Variant Analysis Tool (CVAT). Applying this to 289 clinical exome reports, we compared the performance of junior practitioners with that of experienced medical geneticists and assessed the utility of reported variants.

resultsCVAT enabled performance comparable to that of experienced medical geneticists. In total, 124 of 289 (42.9%) exome reports and 146 of 382 (38.2%) reported variants supported a diagnosis. Overall, 10.5% (1 pathogenic [P] or likely pathogenic [LP] variant and 39 variants of uncertain significance [VUS]) of variants were reported in genes without established disease association; 20.2% (23 P/LP and 54 VUS) were in genes without sufficient phenotypic concordance; 7.3% (15 P/LP and 13 VUS) conflicted with the known molecular disease mechanism; and 24% (91 VUS) had insufficient evidence for deleteriousness.

conclusionImplementation of CVAT standardized clinical interpretation of genomic variation and emphasized the need for collaborative and transparent reporting of genomic variation.

Indexed as

Genetic TestingGenetic VariationExomeExome SequencingGenomicsHumansExome sequencingGenomic medicinePrecision medicineVariant classificationVariant interpretation

Identifiers

PMID35442193
PMCPMC9363005

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.