Maps clinically significant variants by gene and position!
ClinVar is a freely accessible, public archive of reports of the relationships between human variations and phenotypes, with supporting evidence at NLM/NCBI. To help you access your variants of interest quickly, ClinVar is offering an experimental release of an all-new visualization tool in the search results. This graphical display provides an overview of variants when you search by gene or genomic region (Figures 1 and 2).
Currently the graphical display is implemented as an experiment and will appear for only 10 percent of searches by gene or genomic region, but the links in this post will show the display so you can try it out. Alternatively, if you would like to bring up the graphical display for your gene or genomic region search, you can edit the URL in the address bar to change the default gr=0 to gr=1. For example, the following URL with show the graphical display:
https://www.ncbi.nlm.nih.gov/clinvar/?gr=1&term=DSG2[gene]
Note that you can only get the graphical display with gene or genomic region searches. For other types of searches, you will see the table only.
Gene search display
The display for a gene search highlights small variants within the gene. Large structural variants are also marked as a single dot in the middle of the variation. The interactive display shows the placement of variants on the gene and their clinical significance and allows you to zoom in or pan right / left and limit results to variants in a chosen gene. Figure 1 shows the graphical display as it appears at the top of the search results for the desmoglein 2 (DSG2) gene and how to filter and navigate to variants of interest (Search ClinVar: DSG2[gene]).
Figure 1 (A-D). Graphical display views in ClinVar for variants in DSG2, a gene with many known pathogenic variants.
A. Graphical view showing all variants for the DSG2 gene. Results default to the GRCh37 assembly. You can change to the GRCh38 assembly by clicking the arrow at the upper left (circled in red).
B. You can zoom in by mousing over the 8th exon in the gene diagram, which activates a pop-up menu that allows you to re-display only this region by following the link (red box).
C. Refreshed result for the 8th exon of DSG2 showing a number of variants including pathogenic, benign, and ones with conflicting interpretations of pathogenicity. You can select the filters on the left-hand side of the ClinVar result to limit to variants with characteristics of interest, for example Conflicting Interpretations of pathogenicity.
D. Variants in exon 8 of DSG2 filtered for conflicting interpretations of pathogenicity. You can retrieve individual variants by mousing over the graphic to activate the pop-up menu and following the link (red box).
Genomic region search display
The display for a genomic region highlights copy number variations that may span multiple genes. The interactive display shows the placement of small and large variants on the region, classifies them by clinical significance, and allows you to zoom in or pan right / left and limit results to variants in a chosen region. The graphical view also adjusts in response to the standard result filters on the left-hand side. Figure 2 shows the display as it appears for a search for a genomic region, in this case the mu class glutathione S-transferase region on chromosome 1 (Search ClinVar: GRCh37:1:110145000-110290000 ).
Figure 2. The graphical display in ClinVar for a region on chromosome 1 containing the mu class glutathione S-transferase genes. The region view highlights copy number variants (> 1Kb), shown as blue bars for copy number gain and red for copy number loss. Small variants (<1Kb) are shown in the ‘Small variant’ track at the top of the display. As with the gene results, you can filter the display using the filters on the left-hand side and can retrieve individual variants by mousing over the graphic and following the link (red box) in the pop-up menu.
You can access variant records from links on the graphical results by hovering over a particular variant. See the ClinVar documentation for more details on the new display.
Results available on GRCh37 and GRCh38
Results in the graphical display are shown on the GRCh37 assembly by default, but you can easily change to the GRCh38 assembly. When searching by gene, you can change assemblies using the arrow in the top left hand corner of the display (Figure 1 A). When searching by chromosome location, you can include the assembly in the search, for example GRCh38:2:136937000-146682000.
Try it out and let us know what you think!
Please use the ‘Feedback’ button on the bottom right of the ClinVar search results page to provide feedback and to let us know how we can improve the display. You can also write to us directly.
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