Additional features¶
Viewing All Variants¶
If the initial Tiering has not identified any variant(s), GLH users may wish to view all available variants in the patient sample via the “Variants” tab which is split into 3 sub-tabs:
1. Sequence Variants
Shows SNVs and small InDels, and lists the genes with variants detected in the genetic regions defined by the patient's Gene Panels. The list is further filtered according to the project's default Filter Preset. Users can adjust this to view other variants, by selecting a different Filter Preset, and/or selecting the ‘Edit Config’ button on the left-hand side of the variant table
2. Structural Variants
Shows SVs and CNVs. These are filtered by the project’s default SV Filter Preset; filters can be modified.
3. Short Tandem Repeat Variants
Shows STRs in the genetic areas defined by the patient's Gene Panels, or all STRs if no Gene Panels are specified. You can browse the list, or filter it by Gene Panel to highlight variants of interest.
Warning
There is a bug which means that any actions carried out on STRs will not be sent through to the clinical report, users are therefore advised to use the Interpretation Portal for interpretation of STRs and not Congenica. You will be informed once the bug has been fixed.
For additional information about filtering and reviewing variants, please refer to the full Congenica user manual For information about filtering by Genomics England Tiers and Penetrance (not covered in the full User Guide) see Incomplete Penetrance below
Mode of inheritance: Mapping to PanelApp descriptors¶
Congenica uses alternative names to describe the mode of inheritance. Table 2 shows the mapping of the PanelApp Inheritance descriptors to their equivalents in Congenica.
| PanelApp | Congenica |
|---|---|
| Monoallelic, autosomal or pseudoautosomal, (regardless of imprinting status) | Autosomal Dominant |
| Biallelic, autosomal or pseudoautosomal | Autosomal Recessive |
| Both monoallelic and biallelic, autosomal or pseudoautosomal | Autosomal Dominant and Autosomal Recessive |
| Both monoallelic and biallelic, (but biallelic mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | Autosomal Dominant and Autosomal Recessive |
| X-linked (hemizygous in males, biallelic in females) | X-linked |
| X-linked hemizygous mutation in males, may be caused by monoallelic mutations in females | X-linked |
| Mitochondrial | -- not available -- |
Filtering by gene panel and adding new gene panels¶
Gene panels can be used to quickly filter variants in the variant table.
Info
The applied panels, used in the pipeline prioritisation, and their version numbers are viewable at the bottom of the "Overview" page in the "Gene panels" field.
Some panels will have multiple version numbers as defined by the interpretation requests received.
The panels listed by Congenica contain High Evidence or “Green” genes. Those panels listed ending in “LowEvidence” and “ModerateEvidence” correspond to the Red and Amber genes from the indicated panels on PanelApp, respectively.
The gene panels applied for filtering can be modified via the Filters ‘Edit Config’ menu for SNVs, SVs and STRs.
For additional information about variant filtering, please refer to the full Congenica user manual
Adding a new gene panel¶
If the panel required is not present in Congenica, users can add new panels to projects. For more information and instructions on how to do this, please refer to the full Congenica user manual
Note
Users in other GLHs, without access to the project or sub-projects containing the new panels, will not be able to see new panels and their content.
Incomplete Penetrance¶
To support the use of Genomics England’s pipeline to improve Tiering for non-penetrant disorders it is now possible to view the additional Tiering annotations in Congenica.
These annotations are taken from the Interpretation Request and displayed, alongside the Tier, in the appropriate columns in the Variants table and on the table in the Audit tab.
Penetrance annotations are attached to the tier of each variant; variants showing complete penetrance are annotated with CP, variants showing incomplete penetrance are annotated with IP (Figure 22).
Some variants will be annotated with multiple tiers, especially when multiple panels are used to tier the variants. In these cases, hovering over the tier will display the name and version of the gene panel used for tiering (Figure 23). The popup also shows the transcript that was used for tiering - this is the transcript with the most severe predicted variant consequence; it may change depending on the location of the variant, and it may not be the same as the Congenica default transcript.
Filtering by Tier and Penetrance¶
For SNVs and STRs, the filtering options are available in the Filters Edit Config pop-up, present on the left-hand side of the Variants tab. Click on the cog symbol to open the filters configuration menu (Figure 40 shows this for SNVs). For SVs, the filtering options are available directly in the left margin (there is no popup). The Tier and Penetrance filtering options are available in the “Custom” section of the configuration pop-up. As for other filtering options in Congenica, selecting no boxes in this menu will not apply the filter; everything will be shown regardless of tier or penetrance. Selecting all boxes in this menu can be used to filter out any Untiered variants.
Note
For SVs and STRs, ‘TierNull’ is not equivalent to ‘Untiered’**. To view all variants of a given type, all ‘Tier’ filters must be removed. Please refer to Appendix 3 for further information relating to SV Tiering annotations.
Filtering by penetrance can be performed independently of filtering by Tier, or the two filters can be used in combination with each other.
For example:
-
To see only Complete Penetrance variants, regardless of Tier, select Penetrance > Complete.
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To see Tier 3 variants (if the applied panel(s) is removed), regardless of penetrance, select Tier > Tier 3.
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To see Tier 2 variants with Complete Penetrance, select Tier > Tier 2 and Penetrance > Complete.
Click “Update” to apply the filter settings.
