Variant List Germline Small

From this page, users can:

• Review the germline small variants identified by DRAGEN
• Review the additional annotations (e.g. gnomad population frequencies or genotype) 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 (e.g. by tier)
• Flag or add a variant for export
• Add a comment and assign an ACGS classification 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

Key

#	Section	Description
1	Tabs	The different lists of variants available for the case.
2	Filters	Filters applied to the genomic dataset, by default we will show all germline small variants in tier I and III. Click ‘filters’ to see all available filter options.
3	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.
4	Tier and gene	Tier and HGNC gene symbol(s) which the variant affects. We show the affected genes in the highest tier. Genes that are coloured red are tumour suppressor genes, genes that are coloured yellow are oncogenes, blue genes have an ambiguous mode of action. Grey genes have an unknown mode of action.
5	GRCh38 coordinates and Ref > Alt allele	Coordinates of the variant and the nucleotide change of the particular variant within a gene. Clicking the IGV icon will show the variant in IGV.
6	Transcript & protein ID	Contains the Ensembl transcript ID, protein ID, c. and p. HGVS for the canonical transcript.
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	Genotype	Genotype for this variant in this patient. Uses VCF genotype nomenclature where 0 indicates ref allele and 1 indicates alt allele. So 0 / 1 would be heterozygous whereas 1 / 1 would be homozygous for the alt allele
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. ‘PloidyConflict’ Genotype call from variant caller not consistent with chromosome ploidy.
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 documentation for a complete list of QC flags
13	Population frequencies (GEL/gnomAD)	Population germline allele frequency for the variant in GeL and gnomAD dataset.
14	Clinvar	Clinvar ID entry of the variant. Clicking the clinvar icon will show the variant in Clinvar.
15	Classification	The assigned ACGS tiering of a variant. Click the pill to add or edit the classification of a variant.
16	View details	Click this link to navigate to the details page of the variant.
17	Flag a variant	Click this to flag or unflag a particular variant.
18	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.
19	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 tier and coordinates. You can only sort the germline small variant list by tier. To change the order of the variants from ascending to descending follow these steps:

1. Click the green arrow in the tier & gene column
2. The order will change from ascending or descending
3. Click the green arrow again to go back to the default order

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	Tier	Option to show variants within certain Tiers e.g. 1 or 3. Unticking all tier options, will remove any tier filter and include all untiered variants in the list.
4	Quality information	Option to show variants with pass or non pass status as defined by the quality filters of the pipeline.
5	Unselect all	Removes all selected filters
6	Apply filters	Click to see the list of variants with the selected filter settings.

Applying Filters

You can filter the list of germline small variants by several parameters e.g. Tier or pass status. By default we will show all tier 1 and 3 germline 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. The newly selected filters will appear as pills on top of the page

4. Click apply filters

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, filters applied across multiple data items are exclusive e.g. I select Tier 1 and I select 'flagged' in the gene list filter, then I will only see tier 1 variants that are flagged.

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 CommentsClassifyingValidationArtefact Assessment

Adding Comments

You can add comments or classifications to a variant directly in the variant list.

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. Write your comments in 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

To view or add classifications 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 ACGS classification 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.

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Last update: 2023-09-25