4.5 Review

Best practices for the interpretation and reporting of clinical whole genome sequencing

Related references

Note: Only part of the references are listed.
Article Clinical Neurology

Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation study

Kristina Ibanez et al.

Summary: Background repeat expansion disorders caused by short tandem DNA repeats are clinically heterogeneous and difficult to diagnose. A study found that whole genome sequencing shows high accuracy in detecting neurological repeat expansion disorders.

LANCET NEUROLOGY (2022)

Article Biochemistry & Molecular Biology

Successful application of genome sequencing in a diagnostic setting: 1007 index cases from a clinically heterogeneous cohort

Aida M. Bertoli-Avella et al.

Summary: Despite the technical superiority of genome sequencing (GS) over other diagnostic methods, limited studies have been conducted on its clinical application advantages. This study analyzed 1007 consecutive cases where GS was performed clinically, showing a high diagnostic yield and highlighting the importance of GS for ES-negative cases due to its access to noncoding regions and more uniform coverage.

EUROPEAN JOURNAL OF HUMAN GENETICS (2021)

Article Genetics & Heredity

Genome sequencing increases diagnostic yield in clinically diagnosed Alagille syndrome patients with previously negative test results

Ramakrishnan Rajagopalan et al.

Summary: This study aimed to demonstrate the utility of genome sequencing (GS) in diagnosing patients with Alagille syndrome and found four novel pathogenic alterations, increasing the diagnostic yield. GS was able to resolve complex rearrangements, resulting in identification of a pathogenic variant in 97.5% of patients after GS.

GENETICS IN MEDICINE (2021)

Article Biochemistry & Molecular Biology

Opportunistic genomic screening. Recommendations of the European Society of Human Genetics

Guido de Wert et al.

Summary: Genome sequencing in healthcare may lead to opportunistic genomic screening; the European Society of Human Genetics recommends a cautious approach, emphasizing ethical norms and balancing potential benefits against healthcare expenditures; for pediatric genome sequencing, counseling and informed consent should be offered to ensure ethical standards are met.

EUROPEAN JOURNAL OF HUMAN GENETICS (2021)

Article Genetics & Heredity

Australia and New Zealand renal gene panel testing in routine clinical practice of 542 families

Hope A. Tanudisastro et al.

Summary: Genetic testing in nephrology has become routine practice with a growing diagnostic rate, varied likelihood of identifying causative variants based on age and gene panel, and increasing importance in directing treatment, genetic counseling, and family planning.

NPJ GENOMIC MEDICINE (2021)

Article Genetics & Heredity

Expectations and blind spots for structural variation detection from long-read assemblies and short-read genome sequencing technologies

Xuefang Zhao et al.

Summary: Short-read whole-genome sequencing (srWGS) is widely used in large-scale genomics initiatives but faces challenges in detecting structural variants (SVs), overcome by emerging long-read WGS (lrWGS) technologies. The detection power and precision for SV discovery vary significantly by genomic context and variant class.

AMERICAN JOURNAL OF HUMAN GENETICS (2021)

Article Genetics & Heredity

One in seven pathogenic variants can be challenging to detect by NGS: an analysis of 450,000 patients with implications for clinical sensitivity and genetic test implementation

Stephen E. Lincoln et al.

Summary: The study evaluated the impact of technically challenging variants on clinical genetic tests, finding considerable variability in the analytic and clinical sensitivity of NGS workflows. Some challenging variants were not detected by all workflows, highlighting the importance of test design, validation, and selection for clinicians.

GENETICS IN MEDICINE (2021)

Article Genetics & Heredity

Next-generation sequencing for constitutional variants in the clinical laboratory, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Catherine Rehder et al.

Summary: NGS technologies have become established in clinical laboratories, reducing the cost of large-scale sequencing significantly. It is now cost-effective to use these technologies for diagnosing a wide array of clinical scenarios.

GENETICS IN MEDICINE (2021)

Article Genetics & Heredity

Reducing Sanger confirmation testing through false positive prediction algorithms

James M. Holt et al.

Summary: This study evaluated machine learning models trained to identify false positive variants in cGS data to reduce the need for orthogonal testing, showing a significant reduction in confirmatory testing burden while maintaining a low false positive call rate.

GENETICS IN MEDICINE (2021)

Article Genetics & Heredity

Interpretation of mitochondrial tRNA variants

Lee-Jun C. Wong et al.

GENETICS IN MEDICINE (2020)

Article Biochemistry & Molecular Biology

Evaluating Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes

Ana Latorre-Pellicer et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Review Genetics & Heredity

Genomic Data Sharing for Novel Mendelian Disease Gene Discovery: The Matchmaker Exchange

Danielle R. Azzariti et al.

ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 21, 2020 (2020)

Article Multidisciplinary Sciences

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

Nicola Whiffin et al.

NATURE COMMUNICATIONS (2020)

Editorial Material Genetics & Heredity

The Medical Genome Initiative: moving whole-genome sequencing for rare disease diagnosis to the clinic

Christian R. Marshall et al.

GENOME MEDICINE (2020)

Article Multidisciplinary Sciences

A structural variation reference for medical and population genetics

Ryan L. Collins et al.

NATURE (2020)

Article Genetics & Heredity

Clinical and laboratory interpretation of mitochondrial mRNA variants

Lee-Jun C. Wong et al.

HUMAN MUTATION (2020)

Article Genetics & Heredity

Specifications of the ACMG/AMP standards and guidelines for mitochondrial DNA variant interpretation

Elizabeth M. McCormick et al.

HUMAN MUTATION (2020)

Article Multidisciplinary Sciences

Inherited causes of clonal haematopoiesis in 97,691 whole genomes

Alexander G. Bick et al.

NATURE (2020)

Article Biochemical Research Methods

ExpansionHunter: a sequence-graph-based tool to analyze variation in short tandem repeat regions

Egor Dolzhenko et al.

BIOINFORMATICS (2019)

Review Genetics & Heredity

Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases

David Bick et al.

JOURNAL OF MEDICAL GENETICS (2019)

Article Genetics & Heredity

Analyzing and Reanalyzing the Genome: Findings from the MedSeq Project

Kalotina Machini et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2019)

Review Computer Science, Interdisciplinary Applications

Evaluation of the performance of copy number variant prediction tools for the detection of deletions from whole genome sequencing data

Whitney Whitford et al.

JOURNAL OF BIOMEDICAL INFORMATICS (2019)

Article Cell Biology

NUMT Confounding Biases Mitochondrial Heteroplasmy Calls in Favor of the Reference Allele

Hannah Maude et al.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2019)

Editorial Material Genetics & Heredity

PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels

Antonio Rueda Martin et al.

NATURE GENETICS (2019)

Review Genetics & Heredity

Artificial intelligence in clinical and genomic diagnostics

Raquel Dias et al.

GENOME MEDICINE (2019)

Article Biochemistry & Molecular Biology

HmtVar: a new resource for human mitochondrial variations and pathogenicity data

Roberto Preste et al.

NUCLEIC ACIDS RESEARCH (2019)

Article Biochemistry & Molecular Biology

Human Disease Ontology 2018 update: classification, content and workflow expansion

Lynn M. Schriml et al.

NUCLEIC ACIDS RESEARCH (2019)

Article Medicine, Research & Experimental

A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants

Jianling Ji et al.

COLD SPRING HARBOR MOLECULAR CASE STUDIES (2019)

Article Biochemistry & Molecular Biology

ClinVar: improving access to variant interpretations and supporting evidence

Melissa J. Landrum et al.

NUCLEIC ACIDS RESEARCH (2018)

Article Genetics & Heredity

Deep Phenotyping on Electronic Health Records Facilitates Genetic Diagnosis by Clinical Exomes

Jung Hoon Son et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2018)

Article Biochemistry & Molecular Biology

Periodic reanalysis of whole-genome sequencing data enhances the diagnostic advantage over standard clinical genetic testing

Gregory Costain et al.

EUROPEAN JOURNAL OF HUMAN GENETICS (2018)

Article Genetics & Heredity

Updated recommendation for the benign stand-alone ACMG/AMP criterion

Rajarshi Ghosh et al.

HUMAN MUTATION (2018)

Article Medicine, General & Internal

Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease

K. Splinter et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

Article Biochemical Research Methods

Mosdepth: quick coverage calculation for genomes and exomes

Brent S. Pedersen et al.

BIOINFORMATICS (2018)

Article Biochemistry & Molecular Biology

Detection of long repeat expansions from PCR-free whole-genome sequence data

Egor Dolzhenko et al.

GENOME RESEARCH (2017)

Article Medicine, General & Internal

Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation

Jennifer E. Posey et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

Article Genetics & Heredity

Clinical sequencing: is WGS the better WES?

Janine Meienberg et al.

HUMAN GENETICS (2016)

Article Genetics & Heredity

HGVS Recommendations for the Description of Sequence Variants: 2016 Update

Johan T. den Dunnen et al.

HUMAN MUTATION (2016)

Article Biochemical Research Methods

Sambamba: fast processing of NGS alignment formats

Artem Tarasov et al.

BIOINFORMATICS (2015)

Article Genetics & Heredity

The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery

Anthony A. Philippakis et al.

HUMAN MUTATION (2015)

Article Pathology

Confirming Variants in Next-Generation Sequencing Panel Testing by Sanger Sequencing

Linnea M. Baudhuin et al.

JOURNAL OF MOLECULAR DIAGNOSTICS (2015)

Article Multidisciplinary Sciences

Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants

Aziz Belkadi et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2015)

Article Multidisciplinary Sciences

Genome sequencing identifies major causes of severe intellectual disability

Christian Gilissen et al.

NATURE (2014)

Article Genetics & Heredity

PhenoTips: Patient Phenotyping Software for Clinical and Research Use

Marta Girdea et al.

HUMAN MUTATION (2013)

Review Pediatrics

The use of 3D face shape modelling in dysmorphology

Peter Hammond

ARCHIVES OF DISEASE IN CHILDHOOD (2007)

Article Medicine, General & Internal

Association between aplastic anaemia and mutations in telomerase RNA

T Vulliamy et al.

LANCET (2002)