Variant List Somatic SV CNV

From this page, users can:

• Review the somatic structural and copy number Variants (e.g. deletion, loss, gain…) identified by the Canvas and Manta calling methods
• Review the additional annotations (e.g. gnomad population frequencies) for each of these variants
• Review the b-allele frequency, coverage and absolute allele count
• Apply certain filters (e.g. include variants with non-pass status)
• Search for specific variants within a certain chromosome, region or gene
• Sort the list of variants (e.g. by domain, by copy number or by size)
• Flag or add a variant for export
• Add a comment and assign a biological classification or AMP tier to a variant
• Report whether the variant has been tested by another method i.e., Standard of Care Testing
• Report whether a variant is likely to be an artefact or a true variant

Variant Grid GuideSearchingSortingVisualisationsFiltersApplying FiltersRemoving FiltersVariant InterpretationPage Errors

Variant Grid Guide

An overview of the Variant Grid is shown in the following table

Key

#	Section	Description
1	Filters	Filters applied to the genomic dataset, all somatic small variants in domain 1, 2 and 3 are shown. Click ‘filters’ to see all available filter options.
2	Search	Search for variants within specific genomic regions, chromosomes or genes. The format for genomic regions is e.g.17:41196312-41277500 and 17 for chromosomes. Only results within the applied filters will be displayed.
3	Structural Variant Filters	Filters applied to the structural variants, by default all structural variants in domain 1, 2 and 3 are shown. Click ‘filters’ to see all available filter options.
4	Copy Number Variant Filters	Filters applied to the copy number variants, by default all copy number variants in domain 1, 2 and 3 are shown. Click ‘filters’ to see all available filter options.
5	Domain and gene	Domain and HGNC gene symbol(s) which the variant affects. Affected genes in the highest domain are shown by default. Oncogenes are coloured in green, tumour suppressor genes are coloured in blue. Grey genes have an unknown or ambiguous mode of action.
6	GRCh38 coordinates	Coordinates of the variant. Clicking the IGV icon will show the variant in IGV.
7	Chromosomal bands	The cytobands relating to the genomic coordinates of the variant.
8	Variant type / copy number	The variant type e.g., Loss, Gain, Insertion and if applicable copy number of the variant.
9	Size	The length of the variant, shown in Kilobases.
10	Fusion / reading frame	Fused genes and a prediction of the fusion outcome e.g. GENE1:GENE2 - ambigious. Only variants which potentially can produce a gene fusion will show fusion information.
11	Confidence/support	Confidence score of the variant shown by High or Low for copy number variants. Paired and split-red evident for somatic structural variants. A confidence score is shown for variants called by Canvas, paired- and split-read evidence will be shown for variants called by Manta5.
12	VCF filter	Shows whether the variant has passed the pipeline filters. For variants that haven’t passed, the reason is shown in red e.g. ‘q10’ Quality below 10. Only shown for structural variants.
13	QC flag	Flags that indicate a variant with a higher likelihood of being a false positive call or unsubtracted germline variant e.g. ‘GE’ Variants with germline allele frequency >1% in an internal Genomics England dataset. Only shown for structural variants.
14	Population frequencies (GESG/GECG)	Population germline allele frequency for the breakpoints of a given structural variant based on two internal panels of normals: GESG, which consists of germline variants coming from single germline analysis of about 2,200 samples, and GECG, which consists of the variants detected as germline in paired tumour-normal variant calling for about 2,500 cancer samples.
15	Classification	The assigned biological classification and AMP tiering of a variant. Click the pill to add or edit the classification and tiering of a variant.
16	View details	Click to navigate to the details page of the variant.
17	Flag a variant	Click to flag or unflag a particular variant.
18	Add variant for export	Click to add the variant to the export preview. All selected variants will be visible in the export preview page.
19	Comment	Click to add or view comments of the variant. This will open up a drawer on the right side where you view, add or edit all comments assigned to the variant.
20	Origin*	Indication of the variant’s origin as specified by TiNC e.g. Somatic or Uncertain. This will only be available for cases that have gone through the TiNC workflow.

Searching

You can use the search bar to search for variants by gene symbol, coordinates, or chromosome. e.g.:

• TP53
• 17:7660779-7688538
• 17

Searching

Searching will filter the variant list to variants that match the search terms. The plots will also update in accordance with the filtered variant list.

Sorting

By default, all variants are sorted by domain and coordinates. You can sort the list of somatic structural and copy number variants by domain, copy number and size. To change the order of the variants follow these steps:

1. Click three dots in any column with an arrow icon
2. Select the item you want to sort the variant by e.g. size
3. Change the order to ascending or descending by clicking the arrow

Sorting

Only one sort can be activated at the time. By default, we show the first 10 variants sorted by domain and coordinates. To see the remaining variants, scroll to the bottom of the page and new variants will continue to load.

Visualisations

The structural variant, b-allele frequency, coverage and absolute allele count plots are shown by default.

1. To make the visualisations full screen, click the expand icon.
2. To hide the visualisations, click the collapse icon icon.
3. To adjust the width of the plots while maintaining the variant grid, click and drag the light grey vertical divider line between the table and the plots.

Visualisations

Data has been hidden in the above visualisations to protect patient confidentiality.

To get more details about the information in the plots, see Visualiations

Filters

Structural Variant FiltersCopy Number Variant Filters

Structural Variant Filters

Copy Number Variant Filters

Key

#	Section	Description
1	Close icon	Closes the filter panel on the right, changes to the filter settings won’t be applied.
2	Flagged variants	Filter variants based on whether they have been ‘flagged’ or 'unflagged'.
3	Domain	Filter variants by domain e.g. 1, 2 or 3. Removing all domain filterss will show undomained variants.
4	Gene information	Filter by gene information, for example the presence of a gene in the ‘Cancer gene census’ or “National Genomic Test Directory’ gene lists.
5	Quality information	Option to show variants within a certain quality threshold. Number of supporting reads for somatic structural variants. Confidence quality score, high or low for somatic copy number variants.
6	Variant Information	Option to filter on variant information, such as size.
7	Filters coming soon	Details of filters that will be available in future releases.
8	Unselect all	Removes all selected filters.
9	Apply filters	Click to see the list of variants with the selected filter settings.

Applying Filters

The somatic structural and copy number variant list can be filtered by several parameters e.g. variant size, split/paired read support, confidence or presence in gene lists. By default, the variant list is filtered to show all domain 1, 2 and 3 somatic structural and copy number variants that passed the quality checks of the pipeline.

To edit the filters:

1. Click the green filters button on the top left of the page.
2. Edit the filter settings in the filter drawer panel on the right of the screen and click apply filters. For example, apply a minimum size of 5,000kb to structural variants as shown below.
3. The newly applied filters will appear as pills on top of the page.
4. The variant count on the top right will update to show the number of variants visible after filters have been applied. The total number reflects the number of variants the pipeline identified before any quality checks have been applied.

Counts

The count on the top right shows the number of variants remaining after filters have been applied. The total number is the number of variants the pipeline identified before any quality checks have been applied.

Applying Multiple Filters

Multiple filters can be applied at the same time, filters applied across multiple data items are exclusive e.g. I select Domain 1 and I select ‘Acute Myeloid Leukaemia’ in the gene list filter, then I will only see domain 1 variants with genes that are present in the Acute Myeloid Leukaemia gene list in the National Genomic Test Directory.

Removing Filters

Filters can be removed several ways:

1. Click clear filters on the top right of the page
2. Click the ‘x’ in individual pills
3. Click the ‘unselect all’ button in the filters panel and click ‘apply filters’

No Filters Applied

When there are no filters applied or visible, we show all variants with both pass and non-pass status.

Variant Interpretation

Using the interpretation drawer, you can add comments, classifications or tiers to a variant directly in the variant list.

Adding CommentsClassifying and TieringValidationArtefact Assessment

Adding Comments

To view or add comments follow these steps:

1. Click the comment icon on any of the variants
2. A drawer will open on the right
3. Add your comments to the text field and click comment
4. The comment is added and will appear in the history below
5. To edit the comment, click the three dots next to the date and click edit or delete. You can't edit or delete other's comments

Classifying and Tiering

To view or add classifications or tiers follow these steps:

1. Click the green or grey pill in the interpretation column
2. A drawer will open on the right of the screen
3. Click the dropdown arrow and choose the biological classification and/or AMP tier from the menu
4. Click classify
5. The classification is added to the variant and will appear in the history below
6. All classification edits will be stored in the history

Validation

To indicate whether the variant has been validated, follow these steps:

1. Click the comment icon on any of the variants
2. A drawer will open on the right of the screen
3. Under "Validation" click the dropdown arrow and choose the appropriate choice
4. The selection will automatically save
5. The validation information is added to the variant and will appear in the history below
6. All validation edits will be stored in the history

Warning

A bug affecting the interpretation history of the validation means the full history is not being shown, only the latest record. This bug is being investigated and will be fixed in a future release. See Known Issues for further information.

Artefact Assessment

To indicate whether the variant is likely to be a technical artefact or a true variant, follow these steps:

1. Click the comment icon on any of the variants
2. A drawer will open on the right of the screen
3. Under "Artefact assessment" click the dropdown arrow and choose the appropriate choice
4. The selection will automatically save
5. The artefact assessment is added to the variant and will appear in the history below
6. All validation edits will be stored in the history

Warning

A bug affecting the interpretation history of the artefact assessment means the full history is not being shown, only the latest record. This bug is being investigated and will be fixed in a future release. See Known Issues for further information.

Page Errors

When we fail to load the gene data needed for search and gene filters to work, you won’t be able to apply any gene list filters or search by gene. All other information on the page will still be available. When we fail to load all variant data, we will show a full page error. In both cases try reloading the page.

---

Last update: 2023-12-06