1. Home
  2. VarSeq
  3. VarSeq 2.2.4 Known Issues and Work Arounds
  1. Home
  2. VarSeq Known Issues
  3. VarSeq 2.2.4 Known Issues and Work Arounds

VarSeq 2.2.4 Known Issues and Work Arounds

1. LoH X-chromosome calls result in failed CNV analysis.

  • Fix: VarSeq 2.2.4 SP1 and newer will not consider LOH when selecting allosomal targets for computing match scores. Contact support if you would like access to this version.

When computing the Reference Sample Match Score we are excluding any targets that are in an LoH event. However, for male samples the entire chromosome X may be called as an LoH. In the case where a sample does not have targets in the Y chromosome, and sufficient variants in LoH state are detected span all target coverage regions, there will not be any allosomal targets over which to compute the match score for male samples.

This will result in a algorithm error for that sample, (reported in the sample status) and no CNVs will be called.

Work around: Turn off “Normalize sex chromosomes using only controls with matching sex” option of the CNV caller algorithm or remove LOH from the project to not influence normalization.

2. System Error Launching VarSeq 2.2.4 on Windows

For some VarSeq Windows users, when attempting to update VarSeq 2.2.3 to VarSeq 2.2.4 or after installing 2.2.4 on a new machine, an error informs the user that the program cannot start or update because there is a missing Microsoft DLL file.

This new DLL dependency is installed on most machines, but will be bundled in future versions of the product.

Work around: Download and install the missing Microsoft file from the link provided below and then update to VarSeq 2.2.4: https://docs.microsoft.com/en-US/cpp/windows/latest-supported-vc-redist?view=msvc-160#visual-studio-2015-2017-2019-and-2022

3. User Gene Preferences Were not Merging Correctly with System Gene Preferences

In VSClinical, when a user changes the preferred transcript for a gene, changes the inheritance pattern, or the associated disorder the gene preferences file is modified. Typically, data from the user gene preferences and data from the system gene preference is merged and only the data that has changed or differs from the system gene preferences is saved. A gene was dropped from the system gene preferences and as a result, there was missing gene and transcript information from a gene that was also saved from the user gene preferences.

Work around: Send the GenePreferences.gene-pref file to Golden Helix customer support at support@goldenhelix.com. The GenePreferences.gene-pref file can be found by going to Tools-> Open Folder-> Assessment Catalogs Folder.

4. VarSeq Crash in the Match Gene Panel Algorithm

VarSeq was crashing if the project template gene annotation track was not downloaded and there was a match gene panel algorithm in the project. The algorithm was attempting to look up gene names based on gene IDs but cannot perform this task on remote annotation sources.

Work around: Download the latest version of RefSeqGenes
(RefSeqGenes105.20201022v2-NCBI_2020-10-26_GRCh_37_g1k_Homo_sapiens.tsf or RefSeqGenes109.20201120v2-NCBI_2020-11-23_GRCh_38_Homo_sapiens.tsf) before creating any projects. Tools-> Manage Data sources-> search for RefSeq genes, then download the source.

5. ACMG Classifier is Crashing VarSeq due to a Memory Spike When Reading the Reference Sequence

When reading the reference sequence into memory for ACMG Classifier algorithm computation, the memory usage was spiking and causing VarSeq to crash. The ACMG Classifier memory profile was improved by decreasing the cache and removing unnecessary structs.

Work around: Contact Golden Helix customer support at support@goldenhelix.com.

6. gnomAD Genomes v3.1.2 was Missing Quality Flags When Used as a Frequency Track in VSClinical

In the VSClinical Options dialog, when adding gnomAD Genomes v3.1.2 as a custom frequency source, the quality flags were not displaying for variants within an evaluation.

This issue has now been fixed and if any quality flags exist for a variant within the gnomAD genomes v3.1.2 database, they will now display in the VSClinical interface.

Work around: Contact Golden Helix customer support at support@goldenhelix.com.

7. In the VSClinical AMP Workflow, Biomarkers or VUS variants with a Germline Origin Could Not Be Distinguished in a Report

When a variant was added to the AMP workflow as a Germline Suspected variant, and the variant was set to be reported as a biomarker, the variant was being detected as a somatic biomarker and not being detected as a germline origin biomarker in the clinical report . As a result, the classification for germline suspected variants could not be included in a clinical report.

Work around: Contact Golden Helix customer support at support@goldenhelix.com.

8. Timeout When Uploading a Large File to VSWarehouse

The VSWarehouse connection would timeout in the last step of uploading a large file as the VarSeq API request to VSWarehouse would only wait 30 seconds for the API call to resolve. As a resolution, the VarSeq API request to VSWarehouse has been increased to match the 900 second nginx timeout.

Work around: Contact Golden Helix customer support at support@goldenhelix.com.

9. Multiple VSPipeline Instances Writing to the vsprops file was Resulting in Loss of Custom Annotation File Paths

When running multiple VSPipeline instances simultaneously, VSPipeline was competing to write to the vsprops file. The overwriting of this file caused a loss of custom file paths for annotations. To fix this issue, an update flag command was added so VSPipeline cannot change the vsprops file unless this command is passed through the VSPipeline command runner -u/–update.

Work around: Contact Golden Helix customer support at support@goldenhelix.com.

10. Editing Sample Fields Such as Parental Assignment With the Compound Het Algorithm Present Cause VarSeq to Crash

In trio projects that had already computed the Compound Het Algorithm, when sample fields were edited, such as parental assignment, the algorithm would cause the program to crash.

Work around: If sample fields need to be edited, first delete the Compound Het Algorithm, edit the parental assignment, and then add the Compound Het algorithm back into the project.

Updated on January 31, 2022

Was this article helpful?

Related Articles

Leave a Comment