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	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.
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 Tier 1 and Tier 3.
4	Actions	Actions including "View Details" - viewing the variant details page, flagging, adding to export PDF and adding comments.
5	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.
6	GRCh38 coordinates / 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. The reference and Alternate alleles.
7	Transcript & protein ID	Contains the Ensembl transcript ID, protein ID, c. and p. HGVS for the canonical transcript.
8	CDS & protein change	Contains the c. and p. HGVS for the canonical transcript. It is recommended that HGVSp. automated predictions should be double-checked during the interpretation and reporting process, especially for small insertion or deletion variants where a minority of variants may have complex nomenclature varying between prediction tools.
9	Predicted consequences	The predicted consequence types (SO terms) for the canonical transcript.
10	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
11	Alt & Allele read depth	Reads supporting alt allele and total read count.
12	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.
13	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
14	Population frequencies (GEL/gnomAD)	Population germline allele frequency for the variant in GeL and gnomAD exomes dataset.
15	ClinVar	Clinvar ID entry of the variant. Clicking the clinvar icon will show the variant in Clinvar.
16	Classification	The assigned ACGS tiering of a variant. Click the pill to add or edit the classification of a 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. If no variants are returned, there may be no variants in the chromosome, region or gene specified.

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 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	Filter variants based on whether they have been ‘flagged’ or 'unflagged'.
3	Tier	Filter variants by tier e.g. 1 or 3. Removing all tier filters will show undomained variants. 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	Gene Information	Filter varants by gene information, for example by their mode of action e.g., Oncogene or Tumour Supressor Gene.
5	Quality information	Filter variants on quality e.g., variants assigned a PASS or non-PASS status (as defined by the quality filters of the pipeline).
6	Unselect all or Apply filters	Removes all selected filters. Click to apply selected filters to the variant list.

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 and click apply filters.

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

4. 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 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 QualityClassifyingValidationActionabilityComments

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

To view or add classifications follow these steps:

1. Click the dropdown arrow and choose the ACGS classification 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: 2025-03-20