Version 91.1 Updates

We are happy to introduce several enhancements and new features in our latest update:

A new population frequency database, “gnomAD (Exome non-UKB)”, has been added for germline SNP hg38 variants. Similar to the regular “gnomAD (Exome)” database, variant data of “gnomAD (Exome non-UKB)” corresponds to gnomAD v4.1 exome data; however, the new database excludes samples that originate from theUK Biobank (UKB).

“gnomAD (Exome non-UKB)” database is available in the Population Frequencies widget of a variant search page or a variant popup in a case, alongside the other databases, including the regular “gnomAD (Exome)” database:

In a case, “gnomAD (Exome non-UKB)” is also available on the expanded variant tile:

Filtering on this data in the Variants tab is performed by using the “Non-UKB” toggle in the Frequency filter section, under the gnomAD exome subsection. The toggle is OFF by default, and only impacts the four exome filters found in that subsection (i.e. it does not impact other filters, such as the gnomAD genome filters):

Filtering on this data using Filter Decision Trees is performed using four dedicated filters, available under in the Tree Builder the Frequency filter section:

Please note that calculations involving gnomAD data (e.g. gnomAD aggregated frequency, classification rules) are unaffected, i.e. continue to use regular gnomAD exome data where applicable, as before.

Please also note that for hg19 variants, gnomAD 4.1 exome data is not available generally; hence, in hg19 cases, the aforementioned Variants tab “Non-UKB” toggle is disabled. Moreover, in hg19 cases the Filter Decision Trees containing a non-UKB node will not consider the node, i.e. all variants will always pass that node. Finally, in Tree Builder, the non-UKB filter names also include an “hg38” indication (as shown in the above image), serving as a reminder of their intended scope.

You can now export a list of cases from the My Cases page:

Use the new Export button to obtain a spreadsheet containing key case details such as case name and type, applied assay, case creator and status, patient information, and more. The export supports all cases currently displayed, including any filters applied in the My Cases page. The exported file will be sent to your email. This update provides you with the means to document high-level case information for the purpose of traceability, auditing, etc.

In tumor (somatic) cases, region and exon information is now displayed on the variant tile of CNVs, similar to germline cases - the closed CNV tile now displays the variant region and, for CNVs in exonic regions, the exon or exon range as well as the total exon count of the gene. Additionally, in Table View of the Variants tab, the “Region” column is now available, and the “Exon” column properly displays exon information. Finally, also similar to germline cases, for multi-gene CNVs the exon data is not displayed, and hence the variant tile only displays the region information ("Exonic").

This update therefore aligns the display behavior of somatic and germline CNVs and enables easier assessment of exons impacted in somatic cases.

In tumor (somatic) cases, Table View of the Variants tab now displays exon and intron information for fusion variants - the “Exon” column displays exon information for the 5’ breakpoint, as was previously available only for the 3’ breakpoint. Additionally, an “Intron” column has been added, displaying the intron number where applicable. The following image shows examples of different fusions and their exon and intron annotations in Table View:

In the BCOR::BCOR fusion, the 5’ breakpoint is located in exon 2, whereas the 3’ breakpoint is located in intron 1. In the PDE4A:ATN1 fusion, the 5’ breakpoint is located in intron 4, whereas the 3’ breakpoint is located in exon 5. Finally, in the SS18::SS18 fusion, the 5’ breakpoint is located in exon 4, whereas the 3’ breakpoint is located in exon 2.

Resolved an issue where, in organizations that belong to a Group of Organizations (allowing the shared Knowledge Base functionality), comments created on the variant tile did not display under Discussion Topics.