Changelog

v 1.12 (17.06.2024)
General changes:
  • Added updated classification schemes:
    • PALB2: v1.0.0 -> v1.1.0
    • ATM: v1.1.0 -> v1.3.0
    • BRCA1: v1.0.0 -> v1.1.0
    • BRCA2: v1.0.0 -> v1.1.0
  • Previously, moderate benign criteria were colored in pink. Now, very strong benign criteria are shown in this color.
  • Removed extra download for structural variants. Instead they are now combined in one file with small variants. Also, IGV now shows one track for all classified variants.
  • Improved session security
  • Added an API endpoint for access of consensus classifications programmatically
  • Added API documentation
Bugfixes:
  • Selecting pm2_sup in ATM gene specific scheme or bp1_str in BRCA1/2 schemes caused wrong calculated class when selecting another supporting or strong criterium.
  • The force download url for erroneous vcfs was broken
  • Fixed a bug where the header line for annotated literature was incorrectly called 'pubmed' instead of 'literature'
v 1.11 (31.05.2024)
General changes:
  • Update downloads page. Added full data download and database versioning. A new HerediVar full VCF version is calculated every month.
  • Added download archive for previous full VCF downloads
  • Added HerediCaRe upload and improved CliVar upload:
    • Single variants from variant details page
    • Multiple variants from user variant lists page
    • All variants which recieved an update since the last upload from the admin dashboard
  • Updated gene specific PTEN ACMG scheme to v3.1.0
  • The consequences in downloaded vcf files and the variant details page does not contain the pfam protein domain anymore. Instead it was moved to a transcript specific variant annotation field (pfam_domains= in vcf downloads).
  • Moved consequence calculation from VEP to VcfAnnotateConsequence tool from the ngs-bits library GitHub. VcfAnnotateConsequence improves the quality of consequences.
  • Improved the comment that is uploaded to external databases. It now also includes unselected criteria and selected literature.
  • 4M classifications are now uploaded to ClinVar without scheme. Reason: 4M classification is not specified in ACMG spec.
  • Enabled consensus classifications without scheme and their upload to ClinVar.
  • Implemented variant upload to HerediCaRe.
  • Increased security by hardening Keycloak Database and removing popovers with enabled HTML content
  • Added class R (established risk allele) for selection in classifications without scheme
Bugfixes:
  • The variant type search would only show small variants even though both, small and structural variants are selected after querying the second search within a user defined list. This issue was resolved.
  • Previously, the variant search would result in an error when searching for genomic ranges and ticking at least one variant type.
  • Improved genomic range search and its documentation
  • The variant list search was not working properly. This issue was resolved.
  • When a variant did not have an annotation, fetching the annotation status would result in an error.
  • Fixed a bug where the assay quantification was inserted to HerediClassify as a percentage instead of a decimal number.
  • Fixed a bug that caused a variant to not be found when the 'chr' prefix was omitted in the variant string search
  • Fixed a bug that caused variants with multiple genes to not automatically select the best classification scheme
  • Criterium PM5 was previously only moderate strength although the specifications suggest only supporting strength for this criterium in ATM gene specific ACMG scheme. This issue was resolved.
v 1.10.2 (15.04.2024)
Bugfixes:
  • When selecting two or more very strong criteria the resulting class was 3 previously. Now it is 5. Similar with stand-alone criteria.
  • The color of classified variants which only have a consensus classification in HerediCaRe of 3+ or 3- were previously shown in black in IGV. This is fixed now and they are shown with their proper color.
  • Fixed some wording.
v 1.10.1 (12.04.2024)
Bugfixes:
  • Removed empty tab from small variant upload
v 1.10 (12.04.2024)
General changes:
  • When too many variants were added to a user defined variant list the request would previously time out. This has been resolved by adding the variants to the list in the background. A status pill is now shown when the user wants to view a variant list where variants were added from the browse variants table.
  • Updated documentation
  • Activated automatic classification algorithm
  • Added tooltip to criterion select on classify page to explain what the different states mean
  • Added CDH1 ACMG classification scheme
Bugfixes:
  • Fixed a bug where the cancerhotspot annotations would be erroneous: If variants map to the same position in grch38 or are equal when left normalized their cancerhotspots annotations are now summed up
  • Fixed a bug that caused criteria buttons to be unchecked when mutually exclusive criteria were unselected
  • If a variant had multiple HerediCaRe VIDs it would not show the warning in the n_fam and n_pat annotations that the counts might be inaccurate
v 1.9 (12.03.2024)
General changes:
  • Added comments from HerediCaRe center specific classifications
  • Added gnomAD non-cancer scores & faf95 popmax value
Bugfixes:
  • Fixed a bug where the HerediCaRe center specific classifications were not shown when the HerediCaRe consensus classification was unavailable
  • When there were multiple rows in the HerediCaRe classifications table the center details button would always open and close details of all rows
  • Previously, an empty HerediCaRe table was shown on the variant details page when the variant was known to HerediCaRe, but was not classified. The empty table was removed in this case
  • Longer insertions were previously clogging the header line. This was fixed by cropping the reference and alternative bases if their length is large
  • Fixed a bug where vcfs were not downloadable when the variant had HerediCaRe annotations but no center specific classifications
v 1.8.2 (26.02.2024)
!! The automatic classification algorithm is currently under construction. HerediVar is already prepared for it. Thus, you might encounter disabled buttons or dummy data. It will be enabled in a future update
!! Scores from likelihood ratio tests are currently under construction. A simple reannotation is required to show them on HerediVar once they are ready to be downloaded from HerediCaRe.
Bugfixes:
  • Fixed a bug where the SpliceAI score was not shown correctly when it is "."
  • In rare cases the submission condition in ClinVar submissions is na with a description. This case is now handled properly and does not produce erroneous links.
  • Fixed a bug when the assay comment for splicing assays could not be inserted due to length
v 1.8.1 (23.02.2024)
General changes:
  • Changed is_selected for classifications to a more descriptive state information in downloaded vcf files
Bugfixes:
  • Fixed a bug when there were no HerediCaRe center classifications but a consensus classification from HerediCaRe
  • A selected criterium would automatically uncheck if a mutually exclusive criterium was unselected and the mutually exclusive criterium itself is mutually exclusive with the selected criterium
  • Fixed default strength for supporting criteria in ACMG standard scheme
  • Fixed wrapping of PVS1_mod criterium
  • Fixed a bug where the SpliceAI scores would not show on longer indels
v 1.8 (21.02.2024)
General changes:
  • Added scores from likelihood ratio tests.
  • Removed BayesDel annotations from TP53 DB, because they are annotated from a dedicated BayesDel anntation anyway.
  • Improved Cancerhotspots internal representation, display & representation in the INFO column of vcfs
  • Added HerediCaRe center specific classifications
  • Added CSpec BRCA1/2 assays to annotation algorithm
  • Copy evidence of user classifications to a consensus classification now also automatically selects the state correctly
Bugfixes:
  • Fixed a bug where some variants got raw SpliceAI scores instead of the masked ones
  • When constructing an URL for the variant details page it was previously not possible to omit the "chr" prefix for the chromosome
  • Task force protein domains are now shown correctly
  • Transcripts on the negative strand were shown as if they were on the positive strand in the IGV browser
  • Fixed a bug when the user clicked on logout even though the user was already logged out (for example because of inactivity)
  • The default scheme was not properly working. It would automatically select the last scheme in the list as default no matter what was selected on the admin dashboard
  • Fixed a bug when updating ClinVar submissions
  • When selecting any BP criterium the enigma BRCA1/2 schemes would instantly switch to class 2. This is now fixed and only BP1_str triggers class 2
  • Previously the class by scheme was not updated correctly when the user updated their classification
  • Fixed a bug in the criteria column of the automatic classification results that would shrink to width zero when the screen is resized
  • Fixed a bug where unselected criteria where shown as selected for consensus classifications

Changelog

v 1.7 (16.01.2024)
General changes:
  • Added form to create structural variants: DEL, DUP, INV
  • Added structural variants to browse variants table
  • Added START, END, SVTYPE, IMPRECISE info columns to vcf with structural variants
  • Added the general comment to the classified variants download
  • Added a separate download link for all classified structural variants
  • Added structural variants track to IGV
  • Added the coldspot annotation
  • Added variant search which allows the user to search directly for a specific variant using this format: chrom-pos-ref-alt OR chrom-start-end-sv_type in case of structural variants
  • Changed External ID search to overall ID search. It now also allows to search for heredivar variant ids.
  • Update search help
  • Added variant type search option
  • Updated ClinVar to v. 20240207
Bugfixes:
  • Fixed tooltips in browse variant table
  • The annotation service would fail when the variant does not have a dbsnp rsid
  • Fixed a bug that increased the size of the consensus classification label for class 4M
  • The clinvar variation was in the downloaded vcf files twice. Removed one of the copies. The clinvar variation id info is now called "clinvar"
  • In rare cases ClinVar submissions are missing which would result in an error when downloading the vcf file. In such cases the clinvar_submissions info in the downloaded vcf file will be set to None
  • Fixed a bug that prevented the user to change the state of criteria when using microsoft edge
Known issues:
  • HerediCare Center specific classifications are not available
  • HerediCare priors, log likelihood, segregation & cooccurance are not available
v 1.6.1 (11.01.2024)
Bugfixes:
  • Searching for 4M criterium with include_heredicare option would result in an error
  • Searching for class 4 consensus classification with include_heredicare option previously resulted in consensus class 4 and heredicare class 3+
v 1.6 (10.01.2024)
General changes:
  • Classifications can now be submitted without selecting any criterium
  • Added the ClinGen gene specific ACMG classification scheme for ATM
  • Added page to hide classification schemes:
    • disable schemes
    • set default scheme
  • Improved automatic selection of schemes based on genes
  • Changed suffixes from criteria with differing strenghts
  • Download of all classified variants now also contains all variants which were only consensus classified in heredicare. Also added a source of the classification info column
  • Added gnomAD v4 link to variant banner
  • Variant annotations can now be aborted from the admin dashboard
  • Added a button to reannotate all aborted variants from the admin dashboard and moved the reannotate erroneous variants button to the (Re-)annotate tab of the admin dashboard
  • Added automatic classification algorithm v1.0
  • Added the automatic classification result to the browse variant table & variant details page
  • Added automatic classification search
  • Added a button to the admin dashboard to annotate all variants which are missing an annotation
  • Updated VEP from 107.0 to version 110.1
  • Added possibility to "unselect" a criterium when there is evidence that this criterium does not hold
  • Added button to automatically select criteria based on the automatic classification algorithm
  • Added automatic classification algorithm results to vcf export
  • Added flag to vcf export of heredivar classifications if a criterium was selected or not selected in response of evidence
  • Added all external ids to variant vcf export including for example heredicare VIDs, rsids, cosmic ids, etc.
  • Improved display of intergenic variants on variant details page
  • Changed wording in contact form & enabled contact form
Bugfixes:
  • Fixed a bug where the criterium strength addition to the label would reset when the default strength was not its original strength.
  • Fixed the order of selectable criteria strengths on the classify variants page
  • Fixed a bug when submitting 4M classifications
  • Previously, updates to ClinVar submissions were not working & removed the 'customAssertionScore' from ClinVar submissions
  • Fixed a bug when trying to add all variants from a search to a list
  • In BRCA2 v1.0.0 criteria supporting strength was not selectable
  • Sometimes, the classification scheme was not changeable in consensus classifications
v 1.5 (17.11.2023)
General changes:
  • Added option to include heredicare consensus classififcations in consensus classification search
  • Added BayesDEL annotation
  • Improved ClinVar review status & summary display
  • Improved range search. Each range search entry must now be of the format: chrom<sep>start<sep>end. With <sep> being either :, -, space or tabulator. The chromosome number can start with 'chr', but you can also choose to omit it.
  • Added external id search. Which allows to search for external ids like heredicare VIDs, COSMIC COSV ids or dbSNP RSIDs.
  • Added cDNA search
  • Update search help
  • Added COSMIC COSV ids & moved COSMIC links from consequence table to the variant banner.
  • Added GnomAD popmax allele count (AC) annotation
  • Updated documentation
  • Added annotation search
  • The classification comment is now optional
  • REVEL annotations are now transcript specific and show the maximal value in the overview. The details list REVEL scores for all annotations
  • Additional warnings added to annotation service
  • User classifications can now be deleted by the user that created it
  • Renamed class 4 to 4M & changed its color to orange
  • Renamed PALB2 v1.0.0 & TP53 v1.4.0 classification schemes
  • Improved performance of transcript track in IGV
Bugfixes:
  • Fixed a bug where the "gene", "your classification" and "consensus classification" columns were not clickable in the browse variant table
  • Fixed a bug where in some cases some ClinVar submissions were not annotated
  • Fixed a bug which caused some annotations to be erroneous, when importing variants from HerediCare
  • Fixed status of deleted VIDs upon variant import
  • In some cases the consequence was duplicated in the variant banner.
  • Increased the size of the criteria display buttons, because the label did not fit into one line in some cases.
  • Fixed a bug when submitting incomplete information on the "submit to ClinVar" page
Known issues:
  • HerediCare Center specific classifications are not available
  • HerediCare priors, log likelihood, segregation & cooccurance are not available
v 1.4.1 (02.11.2023)
Bugfixes:
  • Fixed a bug where the user was unable to insert classifications by the new ClinGen criteria
v 1.4 (27.10.2023)
General changes:
  • Update landing page
  • Moved previous changelog announcements to a new page
  • The admin dashboard now allows reannotation of a user defined set of databases
  • The admin dashboard now shows an overview of all annotations and annotation errors / warnings
  • Added a contact form where unregistered people can ask a question about a variant
  • Added suffix to criteria names if the selected strength is not the default strength
  • Variants can now be hidden
  • The variant list can now be sorted by chromosomal position and insertion date
  • The page size in the variant list can now be adjusted
  • Consensus classifications are now preselected from the most recent consensus classification for each scheme
  • Added four new ClinGen ENIGMA schemes for specific genes: BRCA1 (v.1.0.0), BRCA2(v.1.0.0), TP53 (v.1.4.0), PALB2 (v.1.0.0)
  • Changed SpliceAI annotations to masked ones
  • Added variant import from HerediCare
  • Added HerediCare number of families and heredicare number of cases annotations
  • Improved criteria popover
  • Added variant import history page
  • Enabled HerediCare annotations in admin dashboard
  • Added downloads page
  • Added variant check page
Bugfixes:
  • Variants are now not selected by default on the search variants page
  • Abbreviations for criteria are now written with upper case letters
  • Disabled criteria were not shown correctly
  • Popovers now stay open when clicked and close when the user does not click inside the popover
  • Fixed a bug where the ClinVar annotation was erroneous which happened when there were missing submissions
  • Fixed a bug where the consequence annotation was erroneous which happened when the variant was large and spanned multiple exons / introns
  • Fixed a bug where the user was unable to download variants which are not annotated
  • Fixed a bug where the user could not search for class 3+
  • The date is now inserted correctly when classifying variants. Preexisting classifications did not change (this is fixed starting from 24.10.23).
Known issues:
  • COSMIC links do not work sometimes
v 1.3 (19.06.2023)
General changes:
  • Added checkboxes to variant table which allows more fine grained collection of variants in lists
  • Added information about the chosen criteria to the comment of a ClinVar submission from HerediVar
  • Updated documentation
  • The strength of all ACMG criteria can be adjusted now
  • Added continuous numbering of variants in variant lists
  • Added 3+ and 3- classes. They can be selected manually from the dropdown
  • Added important variant information to classify page
  • Mane select transcripts are now shown in green in IGV
Bugfixes:
  • Fixed ClinVar uploads
    Classifications are currently submitted to the ClinVar TEST ENDPOINT which is reset periodically! None of your ClinVar submissions will go live at the moment.
  • Fixed a bug when the user tried to access a non existing variant list
  • Improved performance of variant table
  • Fixed a bug where the user was unable to search for gene:hgvs strings in the variant table
  • Classified variants in IGV browser are now shown with the color scheme corresponding to the classification
  • Fixed a bug where some characters were replaced by the url encoding in HGVS strings
  • Fixed a couple of CSP errors
  • Fixed the colors of classified variants in IGV
  • Fixed colors of acmg criteria buttons
Known issues:
  • COSMIC links do not work sometimes
v 1.2 (12.05.2023)
General changes:
  • Improved user registration form
  • Added profile page which allows each user to edit their name, mail and affiliation by themselves
  • Added possibility to search for multiple lists simultaneously
  • Added duplicate, intersect, subtract and union actions for user variant lists
  • Updated documentation
Bugfixes:
  • Fixed a bug where the user was able to upload multi allelic variants
  • Fixed a bug where the user was able to insert invalid variant sequences
  • Navigation is now shown independent of scroll position on documentation page
  • Fixed a bug when searching it would not show any variants
v 1.1 (08.05.2023)
General changes:
  • External links now open a new tab on left click
  • Added documentation
Performance changes:
  • Added client-side pagination of the literature table
v 1.0
Initial release