Variant List Somatic Small

From this page, users can:

• Review the somatic small variants identified by the variant caller Strelka
• Review the additional annotations (e.g. gnomAD, COSMIC and Cancer Hotspots) for each of these variants
• 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 by domain
• 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 GuideSearchingSortingFiltersApplying 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 show up.
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	Domain and gene	Domain and HGNC gene symbol(s) which the variant affects. The 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.
5	GRCh38 coordinates and Ref>Alt Allele	Coordinates of the variant. Clicking the IGV icon will show the variant in IGV. The reference allele and alt allele i.e., C>T.
6	Transcript & Protein ID	Contains the Ensembl transcript ID and protein ID.
7	CDS & protein change	Contains the c. and p. HGVS for the canonical transcript.
8	Predicted consequences	The predicted consequence types (SO terms) for the canonical transcript.
9	VAF	Variant allele frequency (VAF).
10	Alt & Allele read depth	Reads supporting alt allele and total read count.
11	VCF filter	Shows whether the variant has passed the variant caller filters. For variants that haven’t passed, the reason is shown in red e.g. ‘LowDepth’ Tumor or normal sample read depth at this locus is below 2.
12	QC flag	Flags that indicate a variant call may be of a lower quality and at greater risk of being a false positive. Hover over the QC flag for a description. Refer to the variant details documentaiton for a complete list of QC flags.
13*	Origin	Indication of the variant’s origin as specified by TiNC e.g. Somatic or Uncertain. This column will only be shown for cases that have gone through the TiNC workflow.
14	Population frequencies (gnomAD/GeL)	Population germline allele frequency for the variant in gnomAD and internal GeL dataset.
15	COSMIC (version)	Shows whether the variant is found in the COSMIC database version specified. If found, the COSM ID will be displayed alongside a link to the entry, and the number of samples with the variant in brackets.
16	Cancer hotspots	Shows whether the variant is found in the [Cancer Hotspots] database (https://www.cancerhotspots.org/#/home).
17	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.
18	View details	Click this link to navigate to the details page of the variant.
19	Flag a variant	Click this to flag or unflag a particular variant.
20	Add variant for export	Click this to add the variant to the export preview. All selected variants will be visible in the export preview page.
20	Comment	Click this 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.

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

Sorting

By default, all variants are sorted by domain and coordinates. 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. Domain
3. Change the order to ascending or descending by clicking the arrow

Sorting

Only one sort can be activated at the time. By default, the first 20 variants are shown, sorted by domain and coordinates. To view additional variants, continue to scroll to the bottom of the page. Variants will continue to load as you scroll.

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	Option to show variants that have or do not have ‘flagged’ status.
3	Domain	Option to show variants within certain domains e.g. 1,2 or 3. Unticking all domains, will remove any domain filter and include all undomained variants in the list.
4	Gene lists	Option to show variants that affect genes that are present in the ‘Cancer gene census’ or “National Genomic Test Directory’ gene list. You can apply filters for presence in specific clinical indications or tumour groups.
5	Quality information	Option to show variants assigned a PASS or non-PASS status.
6	Variant information	Option to show variants within a certain Variant Allele Frequency range.
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 apply selected filters to the variant list.

Applying Filters

You can filter the list of somatic small variants by several parameters e.g. variant allele frequency (VAF) or presence in gene lists such as the Cancer Gene Census. By default, the variant list is filtered to show all domain 1, 2 and 3 somatic small 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 panel on the right by checking or unchecking certain parameters

3. Click apply filters

4. The newly selected filters will appear as pills on top of the page

5. 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.

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 and filters applied across multiple data items are exclusive e.g. selecting Domain 1 and selecting ‘Acute Myeloid Leukaemia’ in the gene list filter will only show 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, all variants with both pass and non-pass status are shown.

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 gene data fails to load, 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 variant data fails to load, a full page error will be displayed. In both cases try reloading the page.

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Last update: 2023-09-28