This document explains how to use Gene panel builder (GPB) for end users. See also About gene panels for more in-depth explanation of the underlying concepts.
GPB consists of four main pages given in successive order:
- All gene panels (home page): Lists all existing gene panels, including drafts.
- Create or modify a gene panel: Name and description of a gene panel.
- Select genes and regions: Add genes and/or regions to your gene panel.
- Edit gene panel: Change configuration of individual genes and regions and submit the panel.
Log in using your provided credentials (unless GPB is configured otherwise). On the first page "All gene panels" you have two main options:
- To view or modify an existing panel/draft, click the corresponding name in the list.
- To create a new gene panel from scratch, click
Create New Panel.
GPB saves all changes when you navigate to another page or click the
Save button in the top right corner (on relevant pages). There is no "undo" function other than the standard browser controls (
Ctrl/Command+Z), but simply refreshing the page you are on will reset to the state at last save.
Drafts and versions
If the process of creating or modifying a gene panel has been started, but not finished (submitted), the ongoing work will be saved as a draft. The version will then be appended by
-draft. By default, all new gene panels are given initial version
0.0.1-draft, whereas new drafts from existing panels are versioned as a patch (e.g.
1.2.0 --> 1.2.1-draft).
When a draft has been created from an existing panel, both the original and the new draft version will be listed on the front page (e.g.
1.2.1-draft). After a draft has been submitted, any previous versions of the panel are hidden, but can still be accessed by toggling the
Show inactive (old) gene panels button:
To continue with a draft, simply click on it in the list, or choose
Delete to remove it. Note that the latter will only remove the draft and not any submitted panel the draft was based upon.
Note also that it is possible to create multiple drafts from the same panel. These will be versioned with patch increments based on when they were created (e.g.
1.2.2-draft), and changes are not reflected across the drafts, only relative to the original panel. Submitting will delete all drafts, so you should take care to submit the correct version, and delete unnecessary/temporary drafts whenever possible.
View an existing gene panel
When you select an existing gene panel from the list on the "All gene panels" page, you are first presented with a read-only view of that panel. If you want to make changes, click
Create New / Modify Draft (depending on if you view a submitted panel or an ongoing draft).
Add or modify name and description
Create New Panel or
Create New / Modify Draft you will be taken to the "Create or modify a gene panel" page. Here, you need to provide a name and short name for the panel (if not already existing), and optionally a brief description.
The short name is used for tracking versions and must be unique.
Continue ... to proceed to the next page, or
Cancel ... to leave without saving any changes.
Select genes and regions
On the "Select genes and regions for ..." page, you can add genes through existing Genomics England PanelApp panels or directly as individual genes, as well as special regions not defined as a gene. Once you are done, click
Continue ... to proceed to the next page.
Add PanelApp panels
Using PanelApp panels has the advantage of subscribing your panel to subsequent updates from Genomics England. This means that, when updating the gene panel, any genes added to or removed from the PanelApp panel will also be added/removed from your gene panel.
To add a PanelApp panel, search using the ID or name, select it from the results and click
Add. The panel will then be added to a list below the search box.
By default, only genes marked with review status "Green" will be added, but in the list you have the option to also add genes with status "Amber" and "Red":
This can be changed at any time by going back to the "Select genes and regions for ..." page.
To remove a PanelApp panel, click
Remove to the right in the list.
Add individual genes
Instead of using existing PanelApp panels, you also have the option of adding individual genes, either by search or as a list:
- To add an individual gene, search using a gene symbol (existing or alias) or HGNC ID. Select a result in the dropdown and click
Addto add it to your gene panel.
- To add multiple genes, paste a list of genes into the corresponding box and clicking
Add List. Note that the list must contain HGNC IDs only, not gene symbols.
To remove a manually added gene, click
Remove to the right in the list.
PanelApp panels always take precedence. If you try to add an individual gene that is already added through a PanelApp panel, the gene will not be listed under added genes on this page when you save. The gene will still be added, but through the PanelApp association.
If you have a region of interest that isn't contained within the definition and transcript of a gene, you can add any genomic region to the gene panel here. Provide a descriptive name and genomic coordinates and click
Edit configuration of genes and regions
On the "Edit gene panel: ..." page, you can change several parameters for each added gene or region:
Configuration and order of precedence
For both inheritance mode and default transcripts, GPB applies configuration in the following order of precedence:
- Manually set in the present gene panel, using GPB.
- Gene default configuration: Applies across all gene panels. Note this can currently only be changed by a system administrator.
- Automatic using external sources (if available)
- Fallback values
Note that manual changes for a specific gene panel and the gene default configuration are retained through subsequent gene panel updates and will not be automatically replaced by GPB.
GPB automatically populates the inheritance modes for each gene, setting one of:
Unless a default or gene panel-specific configuration has been specified, these values are based on a sanitized sum of inheritance modes reported in OMIM. If no valid inheritance modes are available from OMIM, the fallback value
N/A will be used.
To override a given value for the current gene panel, select a new value from the dropdown. It is recommended to add a comment when doing this.
Default transcript (genes only)
Transcripts are marked with with tags when available:
Default: Specified in the gene default configuration.
MANE Select: Transcript selected by the MANE project.
MANE Plus Clinical: Additional transcript when MANE Select transcript does not cover all clinically relevant variants.
GPB automatically chooses the transcript with the
Default tag, otherwise the
MANE Select and
MANE Plus Clinical transcripts. If no MANE entry is available, GPB chooses the RefSeq transcript with the longest coding frame (if coding), otherwise longest transcription frame.
To override these settings for the current gene panel, select a different transcript in the dropdown. Note that you can select more than one default transcript per gene. It is recommended to add a comment when making changes here.
If a change has been made for the current gene panel (relative to the automatic choice), the cell will be shaded with light green. To filter the column to only show rows where the transcript has changed, click the
Modified only checkbox:
Exclusion (genes only)
Individual genes can be excluded from use in the gene panel without removing it completely. This is the only way of excluding genes added through PanelApp panels (without also removing the PanelApp panel).
You can select multiple reasons for exclusion; note the "Watchlist" option is useful if you want mark a gene for special attention in later revisions; use the search box to quickly locate genes with this label.
Add any notes useful for later revisions here.
The other columns listed in the tables on this page are:
- HGNC ID (genes only)
- Symbol (genes only): Latest symbol available.
- Coverage: The average percentage of base pairs in the currently selected transcript(s) that are covered with reads above a given threshold (e.g. >10x reads) by a given sequencing method (e.g. WGS or WES).
- Exact values will depend on the configuration, which decides if only coding regions are included and whether to include a given numer of bases extending into the introns.
- Low numbers (e.g. <0.90) is indicative that variant calls for (parts of) this transcript will be absent or of low quality for the given method.
- SegDup: The average percentage of exonic base pairs in the currently selected transcript(s) that are covered by a known segmental duplication (as defined by UCSC), with homology exceeding a given threshold (e.g. >=90 % homology).
- Exact values will depend on the configuration, as for coverage.
- Any number >0 here indicate that (parts of) the transcript will have poor variant calling quality.
- Origin: If the gene was added through one or more PanelApp panels, the PanelApp ID(s) and review status for the gene in each panel is shown here.
Detailed information about SegDups (using the same data as GPB) can be found in the UCSC Genome Browser; open the link and turn on the Segmental Dups track under Repeats. Searching by the transcript reference or gene symbol will then give you an overview of any SegDups covering the area, including degree of homology.
Submit a gene panel
When done with editing a gene panel, click
Submit Gene Panel. By default, the gene panel will get a minor version update (e.g.
1.0.0 --> 1.1.0), but you may also choose to make it a major version update (e.g.
1.3.0 --> 2.0.0). Click
Confirm to finish the process. See also Drafts and versions.