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 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 GuideDUX4 FusionsSearchingSortingVisualisationsFiltersApplying 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	Clear Filters	Clear any filters applied to the variant list as shown. By default, the variant list will be filtered to display variants in genes belonging to Domain 1, Domain 2 and Domain 3.
4	Actions	Actions including "View Details" - viewing the variant details page, flagging, adding to export PDF and adding comments.
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. If the genomic coordinates of a structural variant is shown as "Not available", the variant has been called by Pelops which detects the presence of a rearrangement, but not the precise breakpoint coordinates. Consequently, the partner break-end location also cannot be precisely determined, so Pelops returns a 1-2 kb region instead.
7	Chromosomal bands	The cytobands relating to the genomic coordinates of the variant. If the chromosomal bands of a structural variant is shown as "Not available", the variant has been called by Pelops as described above, and a chromsomal band cannot be provided as the precise breakpoint coordinate is unavailable.
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	CNVs will have a confidence value assigned to indicate whether the call is High or Low confidence. All CNVs called by Canvas with a confidence score of >=10 will be labelled as High and <10 labelled as low, while all CNVs called by Dragen with PASS in the VCF filter column will be labelled as High and non-PASS variants labelled as Low. Structural variants called by Manta will have paired- and split-read support shown, while structural variants called by Pelops will have supporting reads per billion shown. Internal tandem duplications in the FLT3 gene called by Pindel will have allele depth support shown.
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. This column is only populated 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. This column is only populated for structural variants. Structural variants called by Pelops will have an ABP (ambiguous breakpoint) flag shown to indicate that it is not possible to determine the fusion breakpoint, and the partner region is returned as a 1-2 kb region instead.
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.
Not shown	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.

DUX4 Fusions

Following the update to Dragen (NGIS release Orion onwards), DUX4 fusions can be called by the Pelops variant caller. These variants will appear differently on the cDSS:

• The genomic coordinates of DUX4 fusions will be shown as "Not available", as Pelops has detected the presence of a rearrangement, but is unable to determine the precise breakpoint coordinate in DUX4. Consequently, the partner break-end location also cannot be precisely determined, so Pelops is returning a 1-2 kb region instead.
• The chromosomal bands will be shown as "Not available", as the precise breakpoint coordinate is unavailable a chromsomal band cannot be provided.
• DUX4 fusions will have an ABP (ambiguous breakpoint) flag shown in the QC flag column, to indicate they are called by Pelops and will not have a genomic coordinate provided for DUX4 and the partner gene will be returned as a 1-2 kb region instead.
• Supporting reads per billion (SRBP) will be provided as a measure of confidence in the confidence/support column.

Dragen v4

PLEASE NOTE: following the pipeline upgrade to Dragen v4, some findings are not UKAS accredited to ISO 15189. Dragen v4 software for calling somatic copy number variants (CNVs) and Pelops algorithm for identifying DUX4 rearrangements are not currently included in the schedule of accreditation issued by UKAS. Please refer to the schedule of accreditation for more information.

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. If no variants are returned, there may be no variants in the chromosome, region or gene specified. The plots will also update in accordance with the filtered variant list.

Gene Search Bug

We have identified a bug when searching the variant list. If a search is performed for a gene e.g., "TGFBR3" and selected from the search box dropdown, then the search bar is cleared and the same gene is searched for again i.e., "TGFBR3", the gene will not display in the search box dropdown a second time. The gene will still display in the variant list when entered into the search bar. Please see the video below illustrates the issue.

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

Warning

We have identified a bug in our plot generation, where genomic sex is being used rather than reported sex. If a cases genomic sex differs from the reported sex, the "expected coverage" line across chrX would display incorrectly.

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 filters will show undomained variants.
4	Gene information	Filter variants by gene information, for example the presence of a gene in the ‘Cancer gene census’ or “National Genomic Test Directory’ gene lists, or the Gene mode of Action e.g., Oncogene or Tumour Supressor Gene.
5	Quality information	Filter variants by 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	Filter variants on particular variant features e.g., size.
7	Unselect all or Apply filters	Removes all selected filters. Click to apply selected filters to the variant list.

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 interpretations and comments corresponding to a variant in the variant list. To open the interpretation drawer, follow these steps:

1. Click the comment icon on any of the variants
2. The interpretation drawer will open on the right of the screen

Variant QualityClassifying and TieringValidationActionabilityComments

Artefact AssessmentArtefact ReasonsArtefact Comment

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

1. Under "Artefact assessment" click the dropdown arrow and choose the appropriate choice
2. The selection will automatically save and the "Saved" icon will appear once saved
3. The artefact assessment is added to the variant and will appear in the history below
4. All artefact assessment edits will be stored in the history

If a variant has been marked as a likely artefact, the interpretation drawer will display this additional field. To indicate the reason why the variant is likely to be a technical artefact, follow these additional steps:

1. Under "Artefact reasons" click the dropdown arrow and choose the appropriate choice from the options shown above
2. The selection will automatically save and the "Saved" icon will appear once saved
3. The artefact reason is added to the variant and will appear in the history below
4. All artefact reason edits will be stored in the history

If a variant has been marked as a likely artefact, the interpretation drawer will display this additional comment box. To add a supporting comment to your artefact assessment, follow these additional steps:

1. Under "Artefact comment" enter the text you wish to include
2. Click "Comment"
3. The artefact comment is added to the variant and will appear in the history below
4. All artefact comment edits will be stored in the history

Warning

Updating the artefact assessment to "True variant" will remove the artefact reasons and comment data from the interpretation drawer but it will still be available in the variant history.

Classifying and Tiering

To view or add classifications or tiers follow these steps:

1. Click the dropdown arrow and choose the biological classification and/or AMP tier from the menu
2. Click classify
3. The classification is added to the variant and will appear in the history below
4. All classification edits will be stored in the history

ValidationAssay TypeAssay Comment

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

1. In the "Validation" section of the interpretation drawer, under "Has this variant or entity been tested by another method (either prior to or following receipt of this WGA)?" click the dropdown arrow and choose the appropriate choice
2. The selection will automatically save and the "Saved" icon will appear once saved
3. The validation information is added to the variant and will appear in the history below
4. All validation edits will be stored in the history

If your previous selection indicated the variant has been validated by another method, an "Assay type" dropdown will appear. To select which assay type(s) the variant has also been detected in, follow these additional steps:

1. Under "Assay Type", click the dropdown arrow and choose the appropriate choices
2. The selection will automatically save and the "Saved" icon will appear once saved
3. The assay type is added to the variant and will appear in the history below
4. All assay type edits will be stored in the history

If your previous selection indicated the variant has been validated by another method, an "Assay comment" box will also appear. To add a comment to support the assay types selected, follow these additional steps:

1. Under "Assay Comment", enter the text you wish to include
2. Click "Comment"
3. The assay comment is added to the variant and will appear in the history below
4. All assay comment edits will be stored in the history

Warning

Updating the validation to a "No" option will remove the assay type and comment data from the interpretation drawer but it will still be available in the variant history.

To enter the type of potential actionability associated with a variant, follow these steps:

1. In the "Actionability" section of the interpretation drawer, under "Type of (potential) actionability:" click the dropdown arrow and choose the appropriate choice(s)
2. The selection will automatically save and the "Saved" icon will appear once saved
3. Optional step: An "actionability comment" box will appear where you can add a comment to support the actionability type entry. If required, add your comments to the text field and click comment
4. Optional step: In the "Actionability" section under "How has/will this potentially actionable variant or entity been/be used?" click the dropdown arrow and choose the appropriate choice. Only one can be selected
5. Optional step: A "Utility comment" box will appear where you can add a comment to support the utility type entry. If required, add your comments to the text field and click comment
6. The actionability information is added to the variant and will appear in the history below
7. All validation edits will be stored in the history

Comments

To view or add comments follow these steps:

1. Add your comments to the text field and click comment
2. The comment is added and will appear in the history below
3. To edit the comment, click the three dots next to the date and click edit or delete. Note you can only edit or delete your own comments, for further information see Recording interpretation

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.

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Last update: 2025-03-11