VSClinical allows for the clinical interpretation of variants based on ACMG & AMP Guidelines

The ACMG/AMP joint guidelines for variant interpretation provide a set of criteria to score variants and place them into one of five classification tiers. Following the guidelines requires deep diving into the annotations, genomic context and existing clinical assertions about every variant. VSClinical provides a tailored workflow to score each relevant criterion while also providing all the bioinformatic, literature and evidence from clinical knowledgebases to assist in the scoring and interpretation process.

VSClinical is designed to allow variant scientists to efficiently process variants. It focuses on the optimal organization and presentation of the ACMG guidelines criteria as questions with supporting evidence and suggested answers. Previous classifications are automatically brought in, focusing effort on the set of novel variants that need to be scored for the first time. Most novel variants will be classified as benign or likely benign, and VSClinical is organized to quickly identify and classify these variants.

The work done in your lab to classify variants will be automatically included in future analyses. As the number of samples processed increases, the number of variants requiring classification will be reduced as well as sample turn-around time. Previously classified variants will be marked with their last evaluation date, allowing them to be accepted in the context of the current sample without extra analysis time. If some critical external data surrounding that variant has changed since it was last evaluated, a flag will be raised to re-evaluate it in the updated context.

While a final classification of a variant requires the manual inspection of the sample’s clinical details, published literature and the content of existing related clinical interpretations, many attributes of a variant and criteria from the ACMG guidelines can be auto-computed with bioinformatic algorithms and specially curated annotation sources. The ACMG auto-classifier algorithm can reduce the complexity of your annotation and filtering process, helping remove benign variants while highlighting potential pathogenic variants.

Any complex process leaves a lot of room for variation of execution by different lab personnel. VSClinical provides a guided workflow that reduces the amount of subjectivity to the variant classification and interpretation process. Standardized questions, automatically computed evidence, and historical context provides the framework for arriving at the final classification consistently and reproducibly.

Learn as You Go

New variant scientists will be able to start classifying variants with confidence using VSClinical’s integrated documentation and best practice excerpts. The guided workflow includes contextual explanations and descriptions of the specialized data sources and evidence brought in to answer scoring questions. We have carefully curated the published literature on ACMG guideline best practices, adaptations and clarifications.

The AMP guidelines for the interpretation of somatic variants provide a set of best practices for evaluating and reporting variants for cancer genomic testing. VSClinical provides a guided workflow for following these best practices, including evaluating the clinical evidence for a reportable biomarker using the AMP Tier evidence levels. VSClinical provides a tailored workflow for interpreting and reporting small variants as well as CNVs and fusions.

• New biomarkers of oncogenic somatic variants, CNVs or fusions will automatically have gene, biomarker and clinical evidence of therapeutic, prognostic and diagnostic response filled in for many common cancers and genes with the professionally curated Golden Helix CancerKB. In many cases, the report will be jump-started with useful genomic background content and well-established clinical evidence. Interpretations include numerous citations, all of which are aggregated in the appendix of the clinical report. Cited on Nature.com

Standardize Lab Workflow

Any complex process leaves a lot of room for variation of execution by different lab personnel. VSClinical provides a guided workflow that reduces the amount of subjectivity to the variant classification and interpretation process. Standardized questions, automatically computed evidence, and historical context provides the framework for arriving at the final classification consistently and reproducibly.

Interpretation Knowledgebase

The work done in your lab to interpret biomarkers will be automatically be reused in future samples. As the number of interpreted biomarkers increases, the number of novel interpretations of clinical evidence will be reduced as well as sample turn-around time. Relevant interpretations done in different tumor types are displayed as reference and as supporting evidence for the current interpretation.

With ACMG For Germline

Variants selected as suspected or confirmed germline in origin follow the complete ACMG guidelines for assessing and report the variants Pathogenicity. Along with a recommendation and auto-computed classification, the ACMG guidelines criteria are presented with supporting bioinformatic evidence and reasons for suggested answers. A separate germline interpretation catalog saves and automatically applies any previous classifications of a variant seen in other samples.

Automate Classification

Evaluating a novel or infrequently observed somatic variant first requires a though classification of the variants impact on the gene and its ability to activate an oncogene or deactivate a tumor suppressor gene. VSClinical implements a somatic auto-classifier that provides immediate feedback on the potential of newly added variants to be Oncogenic. The classification system includes numerous variant-type specific scoring criteria that can be manually reviewed and adjusted.