Towards an evidence-based process for the clinical interpretation of copy number variation

E. R. Riggs, D. M. Church, K. Hanson, V. L. Horner, E. B. Kaminsky, R. M. Kuhn, K. E. Wain, E. S. Williams, S. Aradhya, H. M. Kearney, D. H. Ledbetter, S. T. South, Erik C Thorland, C. L. Martin

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The evidence-based review (EBR) process has been widely used to develop standards for medical decision-making and to explore complex clinical questions. This approach can be applied to genetic tests, such as chromosomal microarrays, in order to assist in the clinical interpretation of certain copy number variants (CNVs), particularly those that are rare, and guide array design for optimal clinical utility. To address these issues, the International Standards for Cytogenomic Arrays Consortium has established an EBR Work Group charged with building a framework to systematically assess the potential clinical relevance of CNVs throughout the genome. This group has developed a rating system enumerating the evidence supporting or refuting dosage sensitivity for individual genes and regions that considers the following criteria: number of causative mutations reported; patterns of inheritance; consistency of phenotype; evidence from large-scale case-control studies; mutational mechanisms; data from public genome variation databases; and expert consensus opinion. The system is designed to be dynamic in nature, with regions being reevaluated periodically to incorporate emerging evidence. The evidence collected will be displayed within a publically available database, and can be used in part to inform clinical laboratory CNV interpretations as well as to guide array design.

Original languageEnglish (US)
Pages (from-to)403-412
Number of pages10
JournalClinical Genetics
Volume81
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

Fingerprint

Genome
Databases
Inheritance Patterns
Expert Testimony
Case-Control Studies
Phenotype
Mutation
Genes
Clinical Decision-Making

Keywords

  • Cytogenetics
  • DNA copy number variation
  • Evidence-based practice
  • Gene dosage
  • Oligonucleotide array sequence analysis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Riggs, E. R., Church, D. M., Hanson, K., Horner, V. L., Kaminsky, E. B., Kuhn, R. M., ... Martin, C. L. (2012). Towards an evidence-based process for the clinical interpretation of copy number variation. Clinical Genetics, 81(5), 403-412. https://doi.org/10.1111/j.1399-0004.2011.01818.x

Towards an evidence-based process for the clinical interpretation of copy number variation. / Riggs, E. R.; Church, D. M.; Hanson, K.; Horner, V. L.; Kaminsky, E. B.; Kuhn, R. M.; Wain, K. E.; Williams, E. S.; Aradhya, S.; Kearney, H. M.; Ledbetter, D. H.; South, S. T.; Thorland, Erik C; Martin, C. L.

In: Clinical Genetics, Vol. 81, No. 5, 05.2012, p. 403-412.

Research output: Contribution to journalArticle

Riggs, ER, Church, DM, Hanson, K, Horner, VL, Kaminsky, EB, Kuhn, RM, Wain, KE, Williams, ES, Aradhya, S, Kearney, HM, Ledbetter, DH, South, ST, Thorland, EC & Martin, CL 2012, 'Towards an evidence-based process for the clinical interpretation of copy number variation', Clinical Genetics, vol. 81, no. 5, pp. 403-412. https://doi.org/10.1111/j.1399-0004.2011.01818.x
Riggs, E. R. ; Church, D. M. ; Hanson, K. ; Horner, V. L. ; Kaminsky, E. B. ; Kuhn, R. M. ; Wain, K. E. ; Williams, E. S. ; Aradhya, S. ; Kearney, H. M. ; Ledbetter, D. H. ; South, S. T. ; Thorland, Erik C ; Martin, C. L. / Towards an evidence-based process for the clinical interpretation of copy number variation. In: Clinical Genetics. 2012 ; Vol. 81, No. 5. pp. 403-412.
@article{d850591d6f304bc7814301f24f46f87e,
title = "Towards an evidence-based process for the clinical interpretation of copy number variation",
abstract = "The evidence-based review (EBR) process has been widely used to develop standards for medical decision-making and to explore complex clinical questions. This approach can be applied to genetic tests, such as chromosomal microarrays, in order to assist in the clinical interpretation of certain copy number variants (CNVs), particularly those that are rare, and guide array design for optimal clinical utility. To address these issues, the International Standards for Cytogenomic Arrays Consortium has established an EBR Work Group charged with building a framework to systematically assess the potential clinical relevance of CNVs throughout the genome. This group has developed a rating system enumerating the evidence supporting or refuting dosage sensitivity for individual genes and regions that considers the following criteria: number of causative mutations reported; patterns of inheritance; consistency of phenotype; evidence from large-scale case-control studies; mutational mechanisms; data from public genome variation databases; and expert consensus opinion. The system is designed to be dynamic in nature, with regions being reevaluated periodically to incorporate emerging evidence. The evidence collected will be displayed within a publically available database, and can be used in part to inform clinical laboratory CNV interpretations as well as to guide array design.",
keywords = "Cytogenetics, DNA copy number variation, Evidence-based practice, Gene dosage, Oligonucleotide array sequence analysis",
author = "Riggs, {E. R.} and Church, {D. M.} and K. Hanson and Horner, {V. L.} and Kaminsky, {E. B.} and Kuhn, {R. M.} and Wain, {K. E.} and Williams, {E. S.} and S. Aradhya and Kearney, {H. M.} and Ledbetter, {D. H.} and South, {S. T.} and Thorland, {Erik C} and Martin, {C. L.}",
year = "2012",
month = "5",
doi = "10.1111/j.1399-0004.2011.01818.x",
language = "English (US)",
volume = "81",
pages = "403--412",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Towards an evidence-based process for the clinical interpretation of copy number variation

AU - Riggs, E. R.

AU - Church, D. M.

AU - Hanson, K.

AU - Horner, V. L.

AU - Kaminsky, E. B.

AU - Kuhn, R. M.

AU - Wain, K. E.

AU - Williams, E. S.

AU - Aradhya, S.

AU - Kearney, H. M.

AU - Ledbetter, D. H.

AU - South, S. T.

AU - Thorland, Erik C

AU - Martin, C. L.

PY - 2012/5

Y1 - 2012/5

N2 - The evidence-based review (EBR) process has been widely used to develop standards for medical decision-making and to explore complex clinical questions. This approach can be applied to genetic tests, such as chromosomal microarrays, in order to assist in the clinical interpretation of certain copy number variants (CNVs), particularly those that are rare, and guide array design for optimal clinical utility. To address these issues, the International Standards for Cytogenomic Arrays Consortium has established an EBR Work Group charged with building a framework to systematically assess the potential clinical relevance of CNVs throughout the genome. This group has developed a rating system enumerating the evidence supporting or refuting dosage sensitivity for individual genes and regions that considers the following criteria: number of causative mutations reported; patterns of inheritance; consistency of phenotype; evidence from large-scale case-control studies; mutational mechanisms; data from public genome variation databases; and expert consensus opinion. The system is designed to be dynamic in nature, with regions being reevaluated periodically to incorporate emerging evidence. The evidence collected will be displayed within a publically available database, and can be used in part to inform clinical laboratory CNV interpretations as well as to guide array design.

AB - The evidence-based review (EBR) process has been widely used to develop standards for medical decision-making and to explore complex clinical questions. This approach can be applied to genetic tests, such as chromosomal microarrays, in order to assist in the clinical interpretation of certain copy number variants (CNVs), particularly those that are rare, and guide array design for optimal clinical utility. To address these issues, the International Standards for Cytogenomic Arrays Consortium has established an EBR Work Group charged with building a framework to systematically assess the potential clinical relevance of CNVs throughout the genome. This group has developed a rating system enumerating the evidence supporting or refuting dosage sensitivity for individual genes and regions that considers the following criteria: number of causative mutations reported; patterns of inheritance; consistency of phenotype; evidence from large-scale case-control studies; mutational mechanisms; data from public genome variation databases; and expert consensus opinion. The system is designed to be dynamic in nature, with regions being reevaluated periodically to incorporate emerging evidence. The evidence collected will be displayed within a publically available database, and can be used in part to inform clinical laboratory CNV interpretations as well as to guide array design.

KW - Cytogenetics

KW - DNA copy number variation

KW - Evidence-based practice

KW - Gene dosage

KW - Oligonucleotide array sequence analysis

UR - http://www.scopus.com/inward/record.url?scp=84859560460&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859560460&partnerID=8YFLogxK

U2 - 10.1111/j.1399-0004.2011.01818.x

DO - 10.1111/j.1399-0004.2011.01818.x

M3 - Article

C2 - 22097934

AN - SCOPUS:84859560460

VL - 81

SP - 403

EP - 412

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 5

ER -