Copy Number Variant Grid¶
This page provides the ability to:
- Sort variants by Tier
- Review the copy number variants identified by DRAGEN CNV
- Review additional annotations and linkouts to external resources for each variant (see CNV Grid Guide below for further details)
CNV grid guide¶
The order of columns in the CNV grid can be changed using the column headers. This will reset to default upon navigating away from the page or on page refresh. 20 variants are shown by default, and more are loaded dynamically when scrolling to the bottom of the page.
Please use the below key in conjunction with the below sections to learn more about the columns in the variant grid.
Key
| # | Section | Description |
|---|---|---|
| 1 | Tier | This can be Tier A, Tier B, Tier Null, or "-" for untiered variants or variants that do not fall within a gene. For further details, please visit the Tier section below. |
| 2 | Genomic region / Cytoband | The genomic region and cytoband of the variants, with a button which displays a linkout to IGV (for read depth investigation). There is also a button that opens a menu containing further links to external databases and resources (DECIPHER (browser), gnomAD CNV, gnomAD SV, UCSC and DGV) for the variant, and a button to copy the variant coordinates in Alamut format |
| 3 | Size (bp) | Length of the copy number variant in base pairs |
| 4 | Type / Copy number | The type of the copy number variant. Loss (deletion CNV) or Gain (duplication CNV). The copy number state is indicated by the number in brackets next to the type |
| 5 | Genes | HGNC gene symbol(s) which the variant affects. We show the first four affected genes (additional genes are indicated wi/th a "+n" pill, with n being the number of genes). Clicking on any gene pill (or +n pill) will open the gene overlay. For further details, please visit the Genes section below. |
| 6 | OMIM associated diseases | Count of associated diseases for the gene in OMIM. For further details, please visit the OMIM section below. |
| 7 | Allele frequency (Loss only) | Frequency track - Displays the percentage of individuals in a reference dataset who carry a copy loss CNV that reciprocally overlaps the query CNV. Reciprocal overlap - Calculated based on CNVs that overlap the query CNV by at least 50% in both directions. These columns will only be populated where the CNV is a copy loss variant - for copy gain variants, a - will be visible. |
| 8 | Individuals with CNV (Gain only) | Frequency track - Displays the percentage of indivduals in a reference dataset who carry a copy gain CNV that reciprocally overlaps the query CNV. Reciprocal overlap - Calculated based on CNVs that overlap the query CNV by at least 50% in both directions. These columns will only be populated where the CNV is a copy gain variant - for copy loss variants, a - will be visible. |
Sorting¶
By default, all variants are sorted by Tier ascending and by variant coordinates. Variants can be sorted by Tier ascending or descending by using the arrow icon or menu in the column headers.
The Tier overlay displays details about the Genomics England Tiering outcome for the variant.
The highest Tier assigned to the variant and the clinical indication for the proband are displayed at the top of the overlay.
Below this we see all prioritisation results (previously known as Report Events) for the variant displayed in a table; the gene, panel, and the variant segregation, inheritance and penetrance considered by Tiering as part of the finding are displayed per prioritisation result.
Key
| # | Section | Description |
|---|---|---|
| 1 | Highest Tier | The highest Tier assigned to the variant by Genomics England Rare Disease Tiering |
| 2 | Clinical indication | The clinical indication for the proband |
| 3 | Tier | Tier assigned by Genomics England Rare Disease Tiering |
| 4 | Entity | Gene or region contained within the CNV for the Genomics England Rare Disease Tiering result |
| 5 | GMS panel name | Name of the GMS panel applied to the patient that is associated with the Genomics England Rare Disease Tiering result, with a link to the GMS signed off PanelApp panel |
| 6 | Links to GEL Rare Disease Genome Analysis Guide | Links to the relevant pages in the Genomics England Rare Disease Genome Analysis Guide |
Genes¶
HGNC gene symbol(s) which the variant affects are displayed in the grid.
When clicking on a gene or "+n" in the 'Genes' column, this opens a gene overlay which displays relevant information for that gene.
Gene overlay¶
The gene overlay which displays relevant information for the gene.
The gene names can be seen along the top of the overlay; a variant can be associated with more than one gene. Gene names are clickable, with each page displaying the relevant information for that gene.
Key
| # | Section | Description |
|---|---|---|
| 1 | Gene name / header | Clickable gene name to navigate between details for each gene |
| 2 | Gene ID | Ensembl gene ID |
| 3 | External links | Linkouts to external resources and databases for the gene (OMIM, PubMed, PanelApp, ClinGen, DECIPHER) |
OMIM associated diseases¶
There is a count of associated diseases in OMIM for each gene visible in the row for the variant.
Clicking the i icon opens the OMIM overlay. Different from the SNV grid, the OMIM overlay in the CNV grid displays all gene-disease associations for the variant, across all genes associated with the variant.
OMIM data that is used for annotating variants will be updated at least every quarter.
OMIM overlay¶
The OMIM overlay displays each disease associated with any gene in OMIM that is associated with the variant, the gene-phenotype mode of inheritance, and a link-out to the OMIM page for each disease (N.B. this is different to the SNV overlay where the associations are displayed for a single gene only). If there is no mode of inheritance in OMIM for an associated disease then Unknown will be visible. The pages of the table can be navigated between using the arrow buttons.
Where a disease is associated with multiple genes for that variant, multiple genes will be displayed next to that disease in the Gene column.
Abbreviations
| Abbreviation | Definition |
|---|---|
| ACGS | Association for Clinical Genomic Science |
| ACMG | American College of Medical Genetics and Genomics |
| CDS | Coding DNA Sequence |
| CNV | Copy Number Variant |
| CVA | Clinical Variant Ark |
| New IB | New Interpretation Browser |
| GEL | Genomics England |
| GMS | Genomic Medicine Service |
| GLH | Genomic Laboratory Hub |
| HGVS | Human Genome Variation Society |
| HTML | Hyper Text Markup Language |
| HSCN | Health and Social Care Network (N3) |
| IGV | Integrative Genomics Viewer |
| IP | Interpretation Portal |
| NGIS | National Genomics Informatics System |
| PID | Patient Identifiable Data |
| QC | Quality Control |
| SO | Sequence Ontology |
| SNV | Single Nucleotide Variant |
| SV | Structural Variant |
| TOMS | Test Order Management Service |
| UAT | User Acceptance Testing |
| VCF | Variant Call Format File |
| WGS | Whole Genome Sequencing |