Background

The Clinical Variant Ark (CVA) is the knowledge base built from NHS Clinical Scientist interpretations of rare disease patients in the 100K Genomes Project and NHS Genomic Medicine Service.

Attention

Variants in CVA are those that have been prioritised by Interpretation Services e.g. Tiering and Exomiser algorithms

CVA provides three mechanisms to access the data in the knowledgebase:

1. A Graphical User Interface - CVA Portal
2. Via a REST API and
3. Via a Python client

CVA Portal

CVA Portal is the GUI that provides access to the knowledgebase, it has 3 main pages:

1. Case View

   Provides an overview of a Rare Disease case in the knowledge base. The overview includes, where available the Summary of Findings (SoFs) and Reporting Outcomes Questionnaires (ROQs) and a list of phenotypically similar cases.

   In addition, it lists all the variants prioritised by the Interpretation Services applied to the case and whether these variants exist in other cases within CVA

2. Variant View

   Provides an overview of variants in CVA and includes the reported ACMG classifications of that variant in cases from the Genomics England Interpretation Platform. From the Variant View you can see all other cases in the Genomics England Interpretation Platform that also have this variant prioritised by Interpretation Services applied to them

3. Gene View

   Gene View provides an overview of all reported variants within a specific gene

How and When Does Data Get Into CVA?

Whole Genome Sequencing (WGS) rare disease analyses from the Genomics England 100K Project and NHS Genomic Medicine Service are automatically registered into CVA.

Results of Interpretation Services e.g. Tiering and Exomiser are added to CVA when they are registered in the CIP-API

Expert interpretations performed by NHS Clinical Scientists are automatically added to CVA in the form of Summary of Findings, Reporting Outcomes Questionnaires and Variant Interpretation Logs (VILs)

Interpreted Genomes

We get any interpretation data when it is registered in CIPAPI e.g. Exomiser and Tiering from the Pipeline and case status is "To be reviewed" (where interpretations are yet to be made).

Summary of Findings

We get SoFs when a user hits submit/save draft in the decision support system (DSS) or in the Interpretation Browser. Once the case's status is in "pending outcomes", SoF is made available automatically in CVA (where an SoF has been generated but the RoQ is yet to be completed).

Reported Outcomes Questionnaires

After an SoF is generated, the user clicks on review and fills the RoQ. Once completed and a user hits 'submit' the case status moves to the "reported cases tab" and it is automatically made available in CVA.

Variant Interpretation Logs

VILs are only available for variants that have an approved decision recorded against them and review completed in Congenica. If a variant has more than one VIL then all VILs are displayed, ordered by timestamp, with the most recently created VIL displayed first. Please note that some older VILs may be missing timestamps.

Time of Day

All data is updated in CVA every day at 4am.

Other Ways to Review Data in CVA

CVA has a REST API and Python client (PyArk) which can be used to programmatically retrieve data

For further information please see here