Principles and Recommendations for Standardizing the Use of the Next-Generation Sequencing Variant File in Clinical Settings.
A national workgroup convened by the Centers for Disease Control and Prevention identified principles and made recommendations for standardizing the description of sequence data contained within the variant file generated during the course of clinical next-generation sequence analysis for diagnosing human heritable conditions. The specifications for variant files were initially developed to be flexible with regard to content representation to support a variety of research applications. This flexibility permits variation with regard to how sequence findings are described and this depends, in part, on the conventions used. For clinical laboratory testing, this poses a problem because these differences can compromise the capability to compare sequence findings among laboratories to confirm results and to query databases to identify clinically relevant variants. To provide for a more consistent representation of sequence findings described within variant files, the workgroup made several recommendations that considered alignment to a common reference sequence, variant caller settings, use of genomic coordinates, and gene and variant naming conventions. These recommendations were considered with regard to the existing variant file specifications presently used in the clinical setting. Adoption of these recommendations is anticipated to reduce the potential for ambiguity in describing sequence findings and facilitate the sharing of genomic data among clinical laboratories and other entities.
Division of Laboratory Systems, Centers for Disease Control and Prevention, Atlanta, Georgia. Electronic address: ilubin@cdc.gov.
Ira M
IM
Lubin
College of American Pathologists, Chicago, Illinois; Kaiser Permanente Research Bank, Oakland, California.
Nazneen
N
Aziz
Partners Healthcare Personalized Medicine, Cambridge, Massachusetts; GeneInsight, a Sunquest Company, Boston, Massachusetts.
Lawrence J
LJ
Babb
Complete Genomics, Mountain View, California.
Dennis
D
Ballinger
Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
Himani
H
Bisht
Personalis, Menlo Park, California; National Center for Biotechnology Information, NIH, Bethesda, Maryland; 10× Genomics, Pleasanton, California.
Deanna M
DM
Church
Complete Genomics, Mountain View, California.
Shaun
S
Cordes
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah.
Karen
K
Eilbeck
Life Technologies, Carlsbad, California.
Fiona
F
Hyland
Division of Laboratory Systems, Centers for Disease Control and Prevention, Atlanta, Georgia.
Lisa
L
Kalman
National Center for Biotechnology Information, NIH, Bethesda, Maryland.
Melissa
M
Landrum
Division of Laboratory Systems, Centers for Disease Control and Prevention, Atlanta, Georgia.
Edward R
ER
Lockhart
National Center for Biotechnology Information, NIH, Bethesda, Maryland.
Donna
D
Maglott
Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, Utah; Boston College, Chestnut Hill, Massachusetts.
Gabor
G
Marth
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
John D
JD
Pfeifer
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Heidi L
HL
Rehm
Division of Molecular and Genomic Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Somak
S
Roy
Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland.
Zivana
Z
Tezak
Complete Genomics, Mountain View, California; Invitae Corporation, San Francisco, California.
Rebecca
R
Truty
Dana-Farber Cancer Institute and Partners Healthcare, Boston, Massachusetts.
Mollie
M
Ullman-Cullere
Department of Pathology, University of Utah and the Institute for Clinical and Experimental Pathology, Associated Regional and University Pathologists Laboratories, Salt Lake City, Utah.
Karl V
KV
Voelkerding
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
Elizabeth A
EA
Worthey
Personal Genome Project, Harvard Medical School, Boston, Massachusetts; Curoverse, Inc., Somerville, Massachusetts.
Alexander W
AW
Zaranek
Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, Maryland.
Justin M
JM
Zook
D030541:Databases, Genetic; D014644:Genetic Variation / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software