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. 2018 Nov;39(11):1614-1622.
doi: 10.1002/humu.23645.

ClinGen Variant Curation Expert Panel experiences and standardized processes for disease and gene-level specification of the ACMG/AMP guidelines for sequence variant interpretation

Edgar A Rivera-Muñoz  1 , Laura V Milko  1 , Steven M Harrison  2   3 , Danielle R Azzariti  2   3 , C Lisa Kurtz  1 , Kristy Lee  1 , Jessica L Mester  4 , Meredith A Weaver  5 , Erin Currey  6 , William Craigen  7 , Charis Eng  8 , Birgit Funke  2   9   10 , Madhuri Hegde  11   12 , Ray E Hershberger  13 , Rong Mao  14   15 , Robert D Steiner  16   17 , Lisa M Vincent  4 , Christa L Martin  18 , Sharon E Plon  7 , Erin Ramos  6 , Heidi L Rehm  2   10   3 , Michael Watson  5 , Jonathan S Berg  1
Affiliations

ClinGen Variant Curation Expert Panel experiences and standardized processes for disease and gene-level specification of the ACMG/AMP guidelines for sequence variant interpretation

Edgar A Rivera-Muñoz et al. Hum Mutat. 2018 Nov.

Abstract

Genome-scale sequencing creates vast amounts of genomic data, increasing the challenge of clinical sequence variant interpretation. The demand for high-quality interpretation requires multiple specialties to join forces to accelerate the interpretation of sequence variant pathogenicity. With over 600 international members including clinicians, researchers, and laboratory diagnosticians, the Clinical Genome Resource (ClinGen), funded by the National Institutes of Health, is forming expert groups to systematically evaluate variants in clinically relevant genes. Here, we describe the first ClinGen variant curation expert panels (VCEPs), development of consistent and streamlined processes for establishing new VCEPs, and creation of standard operating procedures for VCEPs to define application of the ACMG/AMP guidelines for sequence variant interpretation in specific genes or diseases. Additionally, ClinGen has created user interfaces to enhance reliability of curation and a Sequence Variant Interpretation Working Group (SVI WG) to harmonize guideline specifications and ensure consistency between groups. The expansion of VCEPs represents the primary mechanism by which curation of a substantial fraction of genomic variants can be accelerated and ultimately undertaken systematically and comprehensively. We welcome groups to utilize our resources and become involved in our effort to create a publicly accessible, centralized resource for clinically relevant genes and variants.

Keywords: ACMG/AMP guidelines; ClinGen; ClinVar; biocuration; expert panels; sequence variant interpretation.

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Conflict of interest statement

Conflict of interest statement:

R.D.S. is a consultant to and holds stock options in Acer Therapeutics and Censa Pharmaceuticals. C.E. is a member of the External Strategic Advisory Board of N-of-One, and is the pro bono CMO of Family Care Path, Inc. and of PlexSeq Diagnostics/Covariance, Inc.

Several authors are clinical service providers and are employed by laboratories that offer fee-based clinical sequencing. This employment is noted in the author affiliations. {The authors declare no additional conflicts of interest beyond their employment affiliation}

Figures

Figure 1 -
Figure 1 -
Stepwise process for ClinGen Expert Panel application submission and review
See this image and copyright information in PMC

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