VarSome Clinical now includes an Overlap with Known SVs column within the Structural Variant Table. This new feature provides an immediate view of how a copy number variant overlaps with previously reported SVs, supporting faster and more consistent interpretation.
This feature is available for CNV analysis from whole-genome and whole-exome sequencing, as well as tertiary SV analysis from VCF files. Please note that this functionality is currently restricted to CNV variants. Consequently, data will not be available in this column for other types of structural variants, such as insertions or deletions.
Annotations are retrieved from multiple established sources, including ClinVar, DECIPHER, DGV, dbVar, Children’s Mercy Research Institute, the Ira Hall Lab, HPRS, and estd20. These datasets are consolidated to enable direct comparison between your variant of interest and previously reported events.
At A Glance Pathogenicity Inference
The Overlap with Known SVs column displays the highest percentage overlap with a known SV of the same class. An overlap threshold of 70% or greater is applied to define meaningful matches. This threshold supports functional-level comparison, like gene and exon overlap, and improves the reliability of pathogenicity inference.
The column is color-coded based on the predicted pathogenicity inferred from the overlap:
- Green: The SV fully overlaps with, or contains, a known benign or likely benign SV with full gene and exon overlap. The variant is inferred to be benign or likely benign.
- Yellow: The SV overlaps with known benign or pathogenic SV, but only partial gene or exon overlap is present, and therefore, no inference can be made. Yellow is shown when overlapping a variant of uncertain significance or an unclassified SV.
- Red: The SV fully overlaps with, or contains, a known pathogenic or likely pathogenic SV. The variant is inferred to be pathogenic or likely pathogenic.
When hovering over the overlap percentage, users can review detailed information about the corresponding known SV. The tooltip includes:
- Pathogenicity classification of the known SV
- Genomic coordinates
- Source database
- Extent of gene and exon overlap
- Structural relationships, such as identical coordinates or containment
If multiple known SVs overlap, the variant shown in the column corresponds to the highest overlap percentage. Selection is prioritized by pathogenicity. Where overlap percentages are identical, database priority is applied in a predefined order.
Filtering Based on Overlap
Users can filter SVs based on the predicted pathogenicity inferred from the overlaps with known variants of the same class. A custom overlap percentage range can also be obtained.
This allows you to quickly exclude variants predicted to be benign based on strong overlap, reducing the variants that require manual review and streamlining downstream analysis.
Detailed Review in the Overlap with Known SV Card
Selecting the overlaps entry opens the Overlap with Known SV card. This provides detailed information about the prioritized known SVs, as well as all other known SVs that overlap with the variant of interest at lower percentages.
The card also lists all overlapping genes for each known SV. From there, users can navigate directly to gene-level information in VarSome Clinical, supporting deeper clinical assessment.
By linking quantitative overlap, pathogenicity context, and gene-level insight in a single workflow, our Overlap with Known SVs feature strengthens SV interpretation and supports more efficient CNV analysis.
If you'd like to learn more about this, or any of our other features designed to help you focus on the cases that need your expertise the most, get in touch with us at sales@varsome.com to book a consultation. Or feel free to check our website for more information.