15 January 2016
Opal 4.16 is now live!
We are excited to announce the release of ACMG Scoring and Classification within Opal Clinical. Opal Clinical fully supports compliance with the 2015 ACMG Guidelines for interpretation of sequence variants, and accelerates evaluation of the evidence associated with each of the 28 criteria to classify variants.
ACMG Scoring is fully integrated into the standardized clinical interpretation workflows in Opal Clinical. Opal Clinical provides an end-to-end solution for clinical NGS testing, combining Omicia’s industry-leading Opal annotation platform with structured workflows, full support for clinical report generation, curated gene panels and LIS integration -- all within a secure, HIPAA-compliant environment. Contact email@example.com if you’d like to try Opal Clinical.
The American College of Medical Genetics and Genomics' 2015 guidelines1 provide critical standardization and consistency, but can be complex and time consuming to implement. To accelerate and scale interpretation, the ACMG classification guidelines have been fully integrated within Opal’s comprehensive annotation and interpretation workflows.
Opal Clinical’s ACMG Scoring module provides a guided assessment with recommendations, and a simple checkbox evaluation methodology for each criterion. To support the scoring process, Opal Clinical has expanded gene and variant annotations, broader support for condition-gene curation, and more robust citation management for segregation and functional studies.
Opal Clinical's ACMG Scoring module:
- Supports full compliance with 2015 ACMG Guidelines
- Provides a guided assessment with recommendations and simple yes/no evaluation
- Builds your lab's Previously Scored database automatically over time from classified variants
- Saves ACMG criteria assessments for re-use when variant classification is updated, and for audit purposes (“scoring history”)
- Provides expanded annotations and comprehensive support for gene and condition-gene curation
- Enables management of citations for segregation and functional studies, and automatically includes references in the clinical report
In addition, the Opal architecture is flexible, allowing customization of classification rules, enabling labs with existing classification systems, as well as those that have extended the ACMG criteria to further standardize and accelerate their interpretation processes.
1Richards S, Aziz N, Bale S, et al. Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in medicine : official journal of the American College of Medical Genetics. 2015;17(5):405-424. doi:10.1038/gim.2015.30.
Opal's annotations have significantly expanded in this release to better support evaluation of the ACMG criteria. New annotations include:
- Exon IDs
- New ClinVar Evidence match types (for missense variants only): matches codon, matches amino acid
- Repeat Region Track in Gene Viewer (from Ensembl 75)
- VVP now scores mitochondrial variants
NNSplice now calculates the predicted effect of every variant in annotated genes on existing as well as potential splice sites.
Pipeline - VCF Parsing Updates
- Support for spaces in file names and in sample names
- Improved handling of Unicode characters
- AU fields are now handled properly
Data Source & Algorithm Versions
Opal Pipeline 5.1 - Released January 15, 2016
- 1000 Genomes phase 3 version 5 (downloaded May 2, 2013)
- CADD v1.0
- ClinVar (downloaded December 2015)
- COSMIC v71
- dbNSFP version 2.9
- dbSNP release 144
- ENSEMBL version 75
- ExAC 0.3 release
- Exome Variant Server 6500 v0.0.30
- Gene Ontology OBO January 6, 2016
- GERP++ 2010 release
- Genome Reference Consortium Human Genome Build v37
- GWAS catalogue (downloaded May 21, 2014)
- HGMD Public version 7.1
- Human Phenotype Ontology2 build #102
- Human Phenotype Ontology OBO 1697
- MutationTaster (dbNSFP v2.9)
- Omicia Score v2.0
- OMIM (downloaded December 15, 2015)
- PhastCons - phastCons46way (October 8, 2012)
- PhenCode / LSDB (download April 30, 2014)
- PolyPhen-2 v2.2.2 (dbNSFP v2.9)
- SIFT (dbNSFP v2.9)
- SiPhy v0.5
- UMLS version 2015AB (November 12, 2015)
- VAAST Variant Prioritizer v1.0
2Sebastian Köhler, Sandra C Doelken, Christopher J. Mungall, Sebastian Bauer, Helen V. Firth, et al. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data. Nucl. Acids Res. (1 January 2014) 42 (D1): D966-D974 doi:10.1093/nar/gkt1026