SV/CNV Genome browser

The Moon SV/CNV genome browser, which can be opened from the Chromosomal region section within a variant card, displays the genes within and surrounding a SV/CNV variant as well as known dosage-sensitive regions. Clicking any gene in the multi-gene view on top of the screen opens up a gene-level display underneath.

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Multi-gene SV/CNV display

This view shows the structural variant, its encompassing and surrounding genes, and (if present) known haploinsufficient/triplosensitive regions (as curated by ClinGen).

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On top of the screen, the genomic coordinates (chromosome name, start position, and end position) of the SV/CNV event detected in the VCF are shown.

Below, on top of the browser, structural variants are represented by a red (deletion), blue (duplication) or grey (inversion) rectangle. Genes part of the structural variant are displayed inside the coloured area, while surrounding genes are displayed outside.

If present, known dosage-sensitive regions (ClinGen) are represented below the coloured area. Arrows on either side indicate continuity of the region outside the genomic coordinates displayed.

Genes

Disease-associated genes are displayed in dark grey, while non disease-associated genes are displayed in light grey. Hovering over a gene brings up a tooltip with information on:

• Gene name, hyperlinked to the OMIM gene page of interest. If a gene is not available on OMIM, it will be hyperlinked to the corresponding Ensembl gene page.

• For disease-associated genes, the associated disorders and their inheritance (AD: Autosomal dominant, AR: Autosomal recessive, XD: X-linked dominant, XR: X-linked recessive) (based on Apollo).

• Gene-level evidence for dosage sensitivity (No evidence/Little/Some/Sufficient) if available, hyperlinked to the ClinGen page of interest.

• pLI score (only available for GRCh37), hyperlinked to the gnomAD page of interest.

Dosage-sensitive regions

Dosage-sensitive regions curated by ClinGen are annotated in red (haploinsufficient regions) and blue (triplosensitive regions). Clicking the coloured regions redirects you to the ClinGen page of interest. Hovering over a region brings up a tooltip with information on:

• Name of the ClinGen region

• Evidence for dosage pathogenicity (Little/Some/Sufficient) and link to ClinGen page of interest

• Link to relevant publications (PMIDs)

• Link to the OMIM page of interest

Clicking any gene in the multi-gene SV/CNV display opens up a gene-level display below.

Gene-level display

This view shows a high-level overview of the selected transcript of the gene of interest along with the SV/CNV indicator on top.

The gene/transcript is always displayed in the 5' to 3' direction and the visualisation includes UTR regions (light grey boxes), coding exons (dark grey boxes) and intronic regions (dark grey lines).

On top of the screen, the currently visualised gene name and transcript are shown. You can easily change between disease-associated genes within the SV/CNV by selecting the gene name from the drop-down menu next to the gene name. Likewise, you can display the transcript of choice for each gene by selecting it in the drop-down menu.

If present, (likely) pathogenic variants in the gene (from Clinvar or the lab’s internal Knowledge Base) are displayed at the bottom of the gene-level display, colour-coded in yellow and red respectively.

To further explore a gene in more detail, clicking the “Expand” icon opens up a built-in page with the SNV genome browser and its three different levels of visualisation. Clicking the “Expand” icon while pressing the “Command” key, opens up the SNV genome browser in a separate tab.

In the built-in SNV genome browser, grey arrows at the bottom allow to quickly switch the display between the different disease-associated genes part of the SV/CNV. This can also be done by selecting the gene name of interest from the drop-down menu.

For more information on how to explore and move in this level of visualisation, visit the SNV genome browser page.