Manual filtering - CNVs

CNV results are currently visualised on Manual filtering - CNVs tab. 

How to use it

The manual filtering - CNVs tab consists of:

1. A filterable table with all CNV variants annotated by AION. By default the table visualises high quality variants only (see definition of high quality CNV variants here: VCF format | CNV / SV variants VCFs) and is sorted by the rank.

2. A advanced filters filter functionality for creating, editing and applying advanced cascading filter logic with just a few clicks ,see more details Advanced filters

Each variant in the table has a detailed view to inform the user about its clinical relevance through annotations and diseases linked to genes affected by the variant.

CNV annotations

Currently AION visualises and annotates all CNVs with the following information.

Basic variant information annotated

• Type of CNV

• Position

• Zygosity and copy number (CN). The zygosity is deduced from the CN as follows:

  • CN = 0 is a homozygous alternative LOSS

  • CN = 1 is a heterozygous LOSS

  • CN = 2 is the normal copy number

  • CN = 3 is a heterozygous GAIN

  • CN >= 4 is a homozygous alternative GAIN

• Length

• Quality

• Position of the CNV in genome

• Cytoband

• Related genes

• Filter status in AION

• File the variant comes from

Each associated gene is further annotated with;

• Diseases linked to the gene and its

  • Inheritance pattern

  • Symptoms of the diseases and a full comparison to patient symptoms

• Clingen HI/TS dosage sensitivity scores

• pLI, LOEUF, pHaplo, pTriplo

Association to known classified CNVs (pathogenic or benign) from multiple databases. The following sources are used:

• Pathogenic sources;

  • Clinvar

  • Clingen

  • dbVar

• Benign sources;

  • Gnomad SV

  • Clinvar

  • Clingen

  • DDD

  • DGV

  • 1000g

  • CMRI

CNV Visualization

All variants have a link to the IGV desktop application to allow visual exploration of the genomic data. To be able to visualize the data you should have the IGV desktop application open with the corresponding reference genome and relevant BAM files. Additionally, port listening must be enabled and configured to the default port (60151) in the Advanced tab of the View > Preferences window (refer to IGV for more information).