ClinGen's RASopathy Expert Panel consensus methods for variant interpretation

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Bruce D GelbClinGen RASopathy Working Group

Abstract

Standardized and accurate variant assessment is essential for effective medical care. To that end, Clinical Genome (ClinGen) Resource clinical domain working groups (CDWGs) are systematically reviewing disease-associated genes for sufficient evidence to support disease causality and creating disease-specific specifications of American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines for consistent and accurate variant classification. The ClinGen RASopathy CDWG established an expert panel to curate gene information and generate gene- and disease-specific specifications to ACMG-AMP variant classification framework. These specifications were tested by classifying 37 exemplar pathogenic variants plus an additional 66 variants in ClinVar distributed across nine RASopathy genes. RASopathy-related specifications were applied to 16 ACMG-AMP criteria, with 5 also having adjustable strength with availability of additional evidence. Another 5 criteria were deemed not applicable. Key adjustments to minor allele frequency thresholds, multiple de novo occurrence events and/or segregation, and strength adjustments impacted 60% of variant classifications. Unpublished case-level data from partic...Continue Reading

References

Sep 12, 2009·Pharmacogenetics and Genomics·Eric R GamazonNancy J Cox
Jan 15, 2013·Lancet·Amy E RobertsBruce D Gelb
Jul 24, 2013·Annual Review of Genomics and Human Genetics·Katherine A Rauen
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
May 28, 2015·The New England Journal of Medicine·Heidi L RehmUNKNOWN ClinGen
Oct 4, 2015·Nature·UNKNOWN 1000 Genomes Project ConsortiumGonçalo R Abecasis
Jul 15, 2016·Human Molecular Genetics·William E Tidyman, Katherine A Rauen
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Dec 13, 2016·Current Genetic Medicine Reports·William E Tidyman, Katherine A Rauen
Mar 17, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Steven M HarrisonHeidi L Rehm
Apr 14, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Kathryn A PhillipsMichael P Douglas
May 19, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Nicola WhiffinJames S Ware

❮ Previous
Next ❯

Citations

Apr 27, 2018·Human Mutation·Ozge Ceyhan-BirsoyHeather Mason-Suares
Sep 8, 2018·Human Mutation·Ahmad N Abou TayounUNKNOWN ClinGen Sequence Variant Interpretation Working Group (ClinGen SVI)
Jun 28, 2018·Cold Spring Harbor Molecular Case Studies·Andrew R GrantHeidi L Rehm
Oct 13, 2018·Human Mutation·Rajarshi GhoshUNKNOWN ClinGen Sequence Variant Interpretation Working Group
Oct 13, 2018·Human Mutation·Andrea M OzaUNKNOWN ClinGen Hearing Loss Clinical Domain Working Group
Oct 13, 2018·Human Mutation·Melissa J Landrum, Brandi L Kattman
Oct 31, 2018·Journal of Cardiovascular Electrophysiology·Roddy Walsh, Arthur A M Wilde
Jul 11, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Natasha T StrandeJonathan S Berg
Apr 3, 2019·Database : the Journal of Biological Databases and Curation·M L FamigliettiUNKNOWN UniProt Consortium
Mar 7, 2019·Human Mutation·Peter B McGarveyUNKNOWN UniProt Consortium
Feb 21, 2019·Molecular Genetics & Genomic Medicine·Ai-Ling KohEne-Choo Tan
May 1, 2019·Annals of Laboratory Medicine·Young Eun KimMi Ae Jang
Jun 7, 2019·Molecular Diagnosis & Therapy·Susanne B Haga
Jan 19, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Jennifer E PoseyUNKNOWN Centers for Mendelian Genomics
Sep 20, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Tracy BrandtJeanne M Meck
Mar 17, 2020·Current Protocols in Human Genetics·Junyu ZhangJun Shen
Jan 24, 2019·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Annie NiehausHeidi L Rehm
Jun 23, 2019·European Journal of Human Genetics : EJHG·Linnea M BaudhuinSusan A Lagerstedt
Oct 28, 2019·Human Genome Variation·Andrey N GagunashviliVijeya Ganesan
Jan 9, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Jennifer N DinesColin C Pritchard
Apr 21, 2020·Journal of the American Heart Association·Francesco MazzarottoRoddy Walsh
Sep 30, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Brittany M WengerBruce D Gelb
Sep 6, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Laura V MilkoJonathan S Berg
Aug 14, 2020·European Journal of Human Genetics : EJHG·Christina LissewskiMartin Zenker
May 10, 2018·Human Molecular Genetics·Lucila Ohno-MachadoMichael A Hogarth
Apr 14, 2019·European Journal of Human Genetics : EJHG·Terri Patricia McVeighSally Ann Lynch
Sep 4, 2019·Current Protocols in Human Genetics·Steven M HarrisonHeidi L Rehm
Jan 26, 2020·International Journal of Molecular Sciences·Matteo AccetturoAlessandro Stella
Apr 19, 2019·Journal of Clinical Medicine·Chia-Jung LiMeng-Yu Wu
Oct 8, 2020·The New England Journal of Medicine·Teresa N SparksUNKNOWN University of California, San Francisco Center for Maternal–Fetal Precision Medicine
Oct 9, 2020·Journal of Genetic Counseling·Rebecca E VanDykeAmy C Sturm
Oct 22, 2020·European Journal of Human Genetics : EJHG·Julia BrinkmannMartin Zenker

❮ Previous
Next ❯

Methods Mentioned

BETA
Exome Sequencing

Software Mentioned

RASopathy
ClinGen
ClinVar
AMP
Path
LPath
ACMG

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Steven M HarrisonHeidi L Rehm
Genetics in Medicine : Official Journal of the American College of Medical Genetics
Keith NykampScott Topper
© 2022 Meta ULC. All rights reserved