Identification of Medically Actionable Secondary Findings in the 1000 Genomes

PloS One
Emily OlfsonLaura J Bierut

Abstract

The American College of Medical Genetics and Genomics (ACMG) recommends that clinical sequencing laboratories return secondary findings in 56 genes associated with medically actionable conditions. Our goal was to apply a systematic, stringent approach consistent with clinical standards to estimate the prevalence of pathogenic variants associated with such conditions using a diverse sequencing reference sample. Candidate variants in the 56 ACMG genes were selected from Phase 1 of the 1000 Genomes dataset, which contains sequencing information on 1,092 unrelated individuals from across the world. These variants were filtered using the Human Gene Mutation Database (HGMD) Professional version and defined parameters, appraised through literature review, and examined by a clinical laboratory specialist and expert physician. Over 70,000 genetic variants were extracted from the 56 genes, and filtering identified 237 variants annotated as disease causing by HGMD Professional. Literature review and expert evaluation determined that 7 of these variants were pathogenic or likely pathogenic. Furthermore, 5 additional truncating variants not listed as disease causing in HGMD Professional were identified as likely pathogenic. These 12 seconda...Continue Reading

References

Jan 1, 1992·Human Mutation·H H HobbsJ L Goldstein
Oct 1, 1993·Proceedings of the Society for Experimental Biology and Medicine·C S MyersG C Wagner
Jan 1, 1993·The Journal of Clinical Investigation·J A FaginH P Koeffler
Aug 17, 2005·Journal of Cardiovascular Electrophysiology·Srijita Sen-ChowdhryWilliam J McKenna
Jul 13, 2006·JAMA : the Journal of the American Medical Association·Isaac S KohaneRuss B Altman
Nov 6, 2007·The New England Journal of Medicine·Meike W VernooijAad van der Lugt
Apr 17, 2008·Genetics in Medicine : Official Journal of the American College of Medical Genetics·C Sue RichardsUNKNOWN Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee
Jun 13, 2008·The Journal of Law, Medicine & Ethics : a Journal of the American Society of Law, Medicine & Ethics·Susan M WolfBenjamin S Wilfond
Jul 9, 2008·Nature Medicine·Sergey G KuznetsovShyam K Sharan
Oct 28, 2008·Human Mutation·Sharon E PlonUNKNOWN IARC Unclassified Genetic Variants Working Group
Nov 13, 2008·BMJ : British Medical Journal·Jorie VersmissenEric J G Sijbrands
Dec 9, 2008·The American Journal of Bioethics : AJOB·Juli MurphyKathy Hudson
Oct 21, 2009·Circulation·Peter J SchwartzCarla Spazzolini
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Apr 5, 2011·American Journal of Human Genetics·Abel González-Pérez, Nuria López-Bigas
Feb 22, 2012·Science·Daniel G MacArthurChris Tyler-Smith
Mar 10, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Juli Murphy BollingerDavid Kaufman
Apr 7, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Susan M Wolf
Sep 22, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Jonathan S BergJames P Evans
Nov 7, 2012·Nature·UNKNOWN 1000 Genomes Project ConsortiumGil A McVean
Nov 9, 2012·Nature·Monya Baker
May 21, 2013·Science·Amy L McGuireRobert C Green
Jun 22, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Robert C GreenUNKNOWN American College of Medical Genetics and Genomics
Jul 6, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·UNKNOWN American College of Medical Genetics and Genomics
Jul 19, 2013·Circulation. Cardiovascular Genetics·David NgUNKNOWN NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program
Aug 7, 2013·JAMA : the Journal of the American Medical Association·Robert C GreenLeslie G Biesecker
Aug 7, 2013·JAMA : the Journal of the American Medical Association·Lainie Friedman RossEllen Wright Clayton
Aug 7, 2013·JAMA : the Journal of the American Medical Association·Robert KlitzmanWendy Chung
Sep 14, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Barbara J Evans
Sep 24, 2013·American Journal of Human Genetics·Michael O DorschnerGail P Jarvik
Nov 16, 2013·Nucleic Acids Research·Melissa J LandrumDonna R Maglott
Sep 6, 2014·American Journal of Human Genetics·Xin LiStephen B Montgomery

❮ Previous
Next ❯

Citations

Mar 4, 2017·Sports Medicine·Oscar CampuzanoRamon Brugada
Mar 21, 2018·Molecular Genetics and Genomics : MGG·Abhinav JainVinod Scaria
Nov 12, 2018·Molecular Genetics & Genomic Medicine·Lydia D HellwigMauricio J De Castro
Dec 27, 2018·The New England Journal of Medicine·Emily E GroopmanAli G Gharavi
Mar 2, 2019·Journal of Genetic Counseling·Kelly E OrmondSarah S Kalia
Jan 9, 2018·Nature Reviews. Nephrology·Emily E GroopmanAli G Gharavi
Aug 15, 2020·Molecular Genetics & Genomic Medicine·Chieh-Wen KuoNi-Chung Lee
Nov 14, 2018·European Journal of Human Genetics : EJHG·Florence H J van TienenJos L V Broers
Jul 16, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Jeroen van RooijAnnemieke J M H Verkerk
Sep 8, 2016·Human Mutation·Amélie PinardGwenaëlle Collod-Béroud
Jul 19, 2017·Molecular Genetics & Genomic Medicine·Rubén CabanillasJuan Cadiñanos
Jul 27, 2018·Canadian Journal of Kidney Health and Disease·Vinusha KalatharanMatthew B Lanktree
May 29, 2018·Molecular Genetics & Genomic Medicine·Swaroop Aradhya, Robert L Nussbaum
Mar 7, 2019·Clinical Science·Rachel H Horton, Anneke M Lucassen
Jun 18, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·UNKNOWN eMERGE Clinical Annotation Working Group
Jun 14, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Rebecca TrutySwaroop Aradhya
Feb 2, 2019·Aging and Disease·Poyin HuangChing-Kuan Liu
Oct 7, 2018·European Journal of Human Genetics : EJHG·Lonneke Haer-WigmanHelger G Yntema
Oct 6, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·M Ragan HartLucia A Hindorff
Sep 26, 2019·Ear, Nose, & Throat Journal·Atif A AhmedLorien Paulson
Sep 6, 2020·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Emilia Rogoża-JaniszewskaTadeusz Dębniak
Jan 26, 2021·The Canadian Journal of Cardiology·Haran YogasundaramGavin Y Oudit
Nov 22, 2019·The Journal of Molecular Diagnostics : JMD·Erick R ScottStuart A Scott
Dec 17, 2020·Human Mutation·Giovanni BiroloGiuseppe Matullo
Feb 25, 2020·The Journal of Molecular Diagnostics : JMD·Jill HagenkordDavid Bick
May 30, 2021·Journal of Human Genetics·Esra Arslan AteşAhmet Arman
Aug 20, 2021·Frontiers in Cardiovascular Medicine·Wenxi JiangYuan Wang
Sep 2, 2021·American Journal of Medical Genetics. Part a·Megan T LynchBraxton D Mitchell
Aug 25, 2021·Human Mutation·Amal ElfatihXavier Estivill

❮ Previous
Next ❯

Methods Mentioned

BETA
dissections
exome-sequencing
Exome Sequencing

Software Mentioned

Ensembl
Genome Build 19
ClinVar
HGMD Professional
refGene
ensGene
Human Gene Mutation Database ( HGMD ) Professional
UCSC
1000 Genomes Browser
ANNOVAR

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Breast Cancer: BRCA1 & BRCA2

Mutations involving BRCA1, found on chromosome 17, and BRCA2, found on chromosome 13, increase the risk for specific cancers, such as breast cancer. Discover the last research on breast cancer BRCA1 and BRCA2 here.

Aneurysm

Aneurysms are outward distensions or bulges that occurs in a weakened wall of blood vessels. Discover the latest research on aneurysms here.

Adenomatous Polyposis Coli

Adenomatous polyposis coli is a protein encoded by the APC gene and acts as a tumor suppressor. Discover the latest research on adenomatous polyposis coli here.

Cancer -Omics

A variety of different high-throughput technologies can be used to identify the complete catalog of changes that characterize the molecular profile of cohorts of tumor samples. Discover the latest insights gained from cancer 'omics' in this feed.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.

Arrhythmogenic Right Ventricular Dysplasia

Arrhythmogenic right ventricular dysplasia is a congenital cardiomyopathy that is characterized by infiltration of adipose and fibrous tissue into the right ventricle wall and loss of myocardial cells. Primary injuries usually are at the free wall of the right ventricular and right atria resulting in ventricular and supraventricular arrhythmias. Discover the latest research on arrhythmogenic right ventricular dysplasia here.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex, associated with a generally dismal prognosis owing to its aggressive behavior. Here are the latest discoveries pertaining to this disease.

© 2021 Meta ULC. All rights reserved