AION Database - variant classifications

As part of the AION Database (AION DB), classifications recorded by users in AION are automatically stored into AION DB and then available for annotation when analysing the same variant again in another case. This data is then annotated to new cases and can be utilised as additional source of insights when analysing the case.

The AION DB is a private database on a per customer level to store and generate insights. Any information stored is not shared with other accounts. The AION DB contains two types of data:

• Population frequency and other statistics of variants in submitted VCF files.
• Previously classified variants (in a similar fashion how ClinVar works).

For both types of data, only small variants (SNPs and Indels) are currently supported. CNV variants and other will be supported in a future iteration of the functionality.

In this article you will find more information about the variant classification options. The AION DB also stores variant statistics data, please refer to that article for further information (see here).

Variant Classifications

Previous variant classifications are key to generate structured institutional knowledge. Through this method, you can leverage and review previous decisions. Each variant classification action requires a comment by the user to justify the decision.

For small variants variants, AION DB classifications are annotated per nucleotide change on new variants. Therefore,  means, when analysing a variant in AION, you will see any classification from the database for the same variant (defined as: chr-pos-ref-alt). This matching is done independently of zygosity, gene/transcript, disease and inheritance mode.  

Summary of the AION DB classifications are visualised in the footer of variant cards. More detailed information is visualised in the variant classification drawer, which can be opened by selecting Show details.

Previous classifications can also be used for variant filtering, allowing you to efficiently accumulate knowledge. You can leverage AION DB variant statistic and previous classifications for filtering variants in the manual filtering views through either column filters or advanced filters.

Classifying a variant

Recording final decisions of variant pathogenicity can be done through the variant classification flow in AION. Any small variant can be classified in AION, so the same flow applies to variants in the AION ranking and variants in manual filtering tab.

To start recording your decision, select "Add classification" button in the upper right corner of the variant card. 

Selecting Add Classification opens a the variant classification drawer, where you can:

1. Quickly review previous classifications of the same nucleotide change (chr-pos-ref-alt) recorded by any user in your institution. Further context is shown as well, together with the comment from the user who recorded the decision. Importantly, you can easily access the case where the classification was made. 
2. Record a new classification. Since the classification is applied to the nucleotid change, you may apply different classification for the same variant in different contexts. Saving a classification automatically stores it to the AION DB with the related comment, and it will be available to any user in the same institution when analysing the same variant in another case.  

A classification of a variant can be edited at any time. Changes of the classification are logged, and visualised in the drawer.

The classifications that AION allows to give to a specific variant are: Pathogenic, Likely Pathogenic, VUS, VUS to Report, Likely Benign, Benign, Artifact and Other. However, we would discourage using “Other” since this classification as it is not specific category or related to the pathogenicity of the variant and can be difficult the interpretation  of the variant in future by yourself or a team member.

Note! Currently variant classification is not connected to reporting, and variants need to still be selected to reported separately. Please refer to page Generating a report for information related report generation.