Known Issues

All known issues with a fix version have been resolved in the specified release.

Issue	Fix Version
VCF Pass filter is not filtering out non-Pass variants in somatic small, germline small, and somatic SV and CNV variant lists	6.8.0
There are minor discrepancies in the whole genome coverage values in cDSS and HTML	TBC
The total variant counts are discrepant in cDSS and HTML	TBC
Cancer Hotspots are not yet available for splice variants or Indels	TBC
Tooltip for QC flag column name and values in the germline small variant list is not visible	TBC
Clicking on an empty region of the SV chart removes all results from the corresponding variant list	TBC
The value for paired or split reads shows as 'Not applicable' for SVs with no SR/PR support	TBC
The table of alternative transcript IDs is being sorted page wise rather than table wise	TBC
Variants overlapping un-domained/un-tiered genes aren't "searchable" from the variant list page	TBC
Population frequencies from the GnomAD genome studies are displayed on the variant list and variant details page, while the cancer HTML report uses the GnomAD Exome studies	TBC
SV plot legend refers to Canvas CNV caller instead of Manta SV caller	TBC
Low BAF plot resolution for somatic and germline CNV calls to assess the support of some CNV calls	TBC
Gene mode of action is missing in the gene track tooltip on the interactive plots available in somatic SV and CNV variant list page	TBC
Origin field not applicable for CNVs because the current pipeline uses Dragen's somatic CNV detection model, which does not strictly perform germline substraction of CNVs	TBC
Incorrect tooltip is shown for Paired reads and Supporting reads per billion in the variant details page	TBC

Dragen Cases

All cases processed by Dragen v4 (NGIS release Orion) should have the following case disclaimer in the cDSS, however it is currently not shown. This will be fixed in a future release. "The overall ploidy for this sample is estimated to be (derived using Dragen software). Please be aware that copy number variation (gains and losses) are annotated relative to a diploid karyotype and therefore diploid genomic regions will NOT be reported as gains or losses for non-diploid genomes."

Tumour First Cases

Variant filtering for reported variants in tumour first cases in the cDSS may differ from that in HTMLs: in these cases, we apply both somatic and germline prioritisation algorithms to all variants with GEL internal population germline allele frequency under 2%, so all such variants will appear on the cDSS. In the HTMLs and CSV tables, all variants with either GEL internal or gnomAD population germline allele frequency over 1% and no potential effect on cancer predisposition genes (nothing in the "Interpretation as germline" field) are filtered out. We are currently working on fully harmonising the variant lists between cDSS and HTML, and this discrepancy should disappear soon.

Copy Number Variant Coverage Plots

We have identified a bug in our plot generation, where genomic sex is being used rather than reported sex. If a cases genomic sex differs from the reported sex, the "expected coverage" line across chrX would display incorrectly. For further information and an example, see the "Tumour Copy Number Variant Plots" section in Visualisations.

Variant List Searching

We have identified a bug when searching the variant list. If a search is performed for a gene e.g., "TGFBR3" and selected from the search box dropdown, then the search bar is cleared and the same gene is searched for again i.e., "TGFBR3", the gene will not display in the search box dropdown a second time. The gene will still display in the variant list when entered into the search bar. Please see the video below illustrates the issue. For further information and an example, see the "Searching" section in Somatic Small, Germline Small or Somatic Structural and Copy Number variant list documentation.

Cancer loci files

At the time of the ‘Nembus’ release on the 9th October, 6 new loci were added used to annotate additional upstream/downstream variant data for cancer cases. These new loci were not included in cancer DSS. These variants are still visible and reported in the correct domain in cDSS, but they are not specifically annotated as being associated with the 6 new loci, which can still be visualised in IGV or the HTML report. The bug has been fixed as of the 6.4.1 release (13/11/2024) and any cases arriving to the cDSS from this point onwards will be unaffected. If you are interested in these loci and the case arrived to the cDSS between 9/10/2024 and 13/11/2024, please check the HTML report and IGV.

Loci	chr	start	end
TAL1_upstream	1	47232226	47242255
TLX3_upstream	5	171205524	171265681
TLX3_downstream	5	171312140	171349100
ABL1_upstream	9	130708042	130713015
CRLF2_upstream	X	1212650	1217650
BCL11B_enhancer	14	97382000	98876000

Please report any bugs or issues with the DSS via the Genomics England Service Desk.