Structural Variants

This article describes all columns in the Structural Variants tab of the Variants table and all associated options of the Filters menu. This table is used to display the SVs in Clinical Reporter in the Variant Selection and Variant Interpretation pages and in Variant Miner.

Actions other than filtering are module specific and described in the articles for each page using the table.

Variants Table

Most columns for the Structural Variants tab of the Variants table are always displayed, with some only available in Clinical Reporter as indicated below. The columns are sortable, unless otherwise noted here, and the current sort order is indicated by gray shading in the header. The default sort order is by chromosome and position.

Checkbox

Click the checkbox to the left of a variant to select or unselect it. To select or unselect all variants visible on the current page click on the checkbox in the table header.

Not available in all views. Not sortable.

Review Priority

The Review Priority field provides a visual prioritization of structural variants based on three criteria: Overlap with evidence, Genes affected and Size. Mousing over the Review Priority field provides a key to the coloring of the data elements.

Click on the column in the table header to sort all variants by Review Priority with higher pathogenicity at the top. Click again to invert the sort order.

Variant

This column provides the Type, ID and Event information for the structural variant imported from the VCF file. 

Type

The values for Type can be CNV, Insertion, Deletion, Duplication, Inversion, or Breakend. For definitions for Breakends please see the VCF format specifications.  Clicking on the Variant column header will sort the variants by Type.

ID

ID for the variant if provided in the VCF file.

Event

An Event ID, if provided in the VCF file, for variants with the Type Breakend.

Position

Position of the variant in the format chr:start-end. Click on the hyperlink to view this position in the UCSC genome browser.

Overlapping SNVs & InDels

Clicking on Overlapping SNVs & InDels to opens the SNVs and InDels tab for this report with the Filters menu Chromosome set to the start and end position of this structural variant, displaying only small variant in this region.

IGV Browser

If the BAM Browser Link is configured for the workspace and IGV installed and open, clicking on the IGV Browser hyperlink moves the browser view to this position.

AV Link

If the Alamut Link is configured for the workspace, clicking on the AV link in the top right corner to link out to Alamut.

Contact support@fabricgenomics.com to enable IGV and Alamut link outs.

Size

The length of the structural variant in KB.

Genes Affected

This column displays a list of gene that are affected by the structural variant. For Panel tests in Clinical Reporter only genes in the panel are displayed. In Variant Miner clicking on the gene symbols will open the Gene and Regulatory Region Overlap dialog with more detailed information on the affected genes. In Clinical Reporter the same information is presented as part of the Variant Detail view.

Not sortable.

Zygosity

A graphical display of the genotype of the variant. The variant allele is represented by a full circle.

Overlap

For tests including family members an Overlap column is added for each member other than the proband. The overlap indicated what percentage of the family member's structural variant overlaps with the proband's structural variant. If the variant is not present in a family member the field is empty.

Not sortable.

Quality  GQ

The fields in this column are composed of three different quality metrics that are extracted from the VCF file. Missing quality metrics are represented by '-'.

Quality

The QUAL value from the VCF file is a Phred-like score measuring the confidence that the position is not homozygous reference.

GQ

The FORMAT tag GQ (Genotype Quality) is a Phred-like score measuring the confidence in the called genotype. The GQ value is color coded:

GQ >= 20

GQ < 20

Evidence 

Literature evidence gathered from DGV, CGDS, dbVar. Click on the icons to display detailed information on the evidence.

Not sortable.

Class

Only in Clinical Reporter.

This column indicates the Clinical Classification assigned to the variant in this report from Variant Scoring: Pathogenic, Likely Pathogenic, Uncertain Significance, Likely Benign, and Benign, as well as any customer defined classifications. For more information on custom classifications please contact Customer Support at support@fabricgenomics.com.

The condition associated with this classification is displayed in parentheses.

Scoring Status

Only in Clinical Reporter.

This column indicates the Scoring Status for a variant. For a variant that has never been scored before this field will be empty.

Overlap with Previously Scored

The variant overlaps with another variant that was classified and finalized as scored in another patient report in this workspace.

Scoring

Evidence review and scoring process has started but the classification has not been finalized yet.

Scored

The variant has been finalized as Scored for this report, see Scoring Variants for details on the scoring process.

Confirmation Status

Only in Clinical Reporter.

The dropdown menu for each variant enables tracking of variant confirmation with alternative technologies:

To Be Confirmed

Choose this option to mark a variant for confirmation. Only variants marked with this confirmation status will be exported with the Export Variants To Be Confirmed option from the Actions menu on the Clinical Reports page.

Confirmed

Indicates successful confirmation of the variant for this sample.

Failed Confirmation

Indicates the variant could not be confirmed for this sample.

No Status

Default if now other status is selected.

Additionally, up to 4 custom Confirmation Statuses can be defined. For more information please contact Customer Support at support@fabricgenomics.com.

Report Section

Only in Clinical Reporter.

Here the section of the Clinical Report in which a scored variant will be reported in is specified as either Primary Findings, Secondary Findings or Not Reported.

Filters Menu

The filtering options available vary by module and test and depend on the columns in the Structural Variants tab of the Variants table. By default no filters are preselected.

Gene Symbol

Enter gene symbol(s) to display only variants in those genes.

Report Filters

Only available in Clinical Reporter, this menu provides options to filter the variants by their status in this report:

Scoring Status

Dropdown menu to filter the variants by the Scoring Statuses All, Scoring, Scored, Previously Scored, or No Status.

Class

Dropdown menu to filter the variants by their clinical classification for this sample. Besides the default classes All, Pathogenic, Likely Pathogenic, Uncertain Significance, Likely Benign, Benign, or No Class (not classified yet), any customer defined classes can be filtered on.

Confirmation Status

This menu allows to filter variants by their confirmation status. Besides the default option All, To Be Confirmed, Confirmed, Failed Confirmation, No Status and Any with Status, customer defined statuses are available as well.

Latest Classification

This menu allows to filter variants by their latest classification. Besides the default classes All, Pathogenic, Likely Pathogenic, Uncertain Significance, Likely Benign, Benign, or No Class (not classified yet), any customer defined classes can be filtered on as well.

Panel

This dropdown menu enables filtering structural variants by a gene panel from Panel Builder. This option is not available for Panel tests in Clinical Reporter or for research workspaces. Only structural variants that overlap with a gene in the panel will be displayed.

Location

You can filter based on chromosome and location within the chromosome, and you can also specify whether you want to filter for regions of homozygosity that are greater than 5MB, 3MB, or 1MB.

Type

Dropdown menu to filter the structural variants by their Type. Options are Any, CNV, Deletion, Insertion, Duplication, Inversion, and Breakend.

Size

Enter values to set a minimum and maximum cutoff to filter structural variants by size.

Require Overlap 

The Require Overlap allows you display only structural variants that overlap with record in DBVar, DGV, and/or ClinGen Dosage Sensitivity.

Inheritance

The Inheritance filter has two options: All and De novo. When you filter for “de novo”, only variants with 0% overlap with both parents are displayed. Note that the “de novo” filter is available only in family cases where there is at least a true trio.