[Decipher-announce] DECIPHER August 2022 Update

Dear All, Greetings from a dry and humid East Anglia. In this update: - DECIPHER v11.14 Released o pHaplo and pTriplo scores § Display of new scores § Removal of %HI scores § Updated dose sensitivity scores and sampling probabilities o ACMG secondary findings v3.1 o Order of gene/disease association resources on gene pages - Update to DECIPHER's consent and assent forms - transition to EBI - Inactive DECIPHER Accounts DECIPHER v11.14 Released ============= You can also view this on the web at: https://www.deciphergenomics.org/about/news pHaplo (deletion intolerance) and pTriplo (duplication intolerance) scores from the recent Collins et al., Cell paper (https://europepmc.org/article/MED/35917817) are now displayed in DECIPHER. These predictive scores are from an analysis of large rare copy-number variants and will assist in the identification of haploinsufficient and triplosensitive genes, supporting accurate variant interpretation. These scores are displayed on the clinical tab on gene pages and gene tables (example here: https://www.deciphergenomics.org/patient/401741/genotype/181219/genes). Genes can also be coloured according to pHaplo or pTriplo scores in the genome browser genes track. pHaplo will be the default colouring for the genes track except for when viewing duplications and other copy-number gains, in which case pTriplo will be used. Please note, genome browser configurations for the genes track for logged-in users have been reset to allow these default settings to be displayed. CNV dosage sensitivity (DS) scores have been updated and are now calculated based on the pHaplo scores of individual genes within a deletion, or pTriplo scores of individual genes within a duplication (or other copy-number gain). Sampling probabilities (an estimate of the proportion of the general population that carry a rare deletion/duplication with a DS score as severe, or more severe than for the CNV being assessed) have also been updated. DS scores were previously calculated using pHI scores (Huang et al., 2010; https://europepmc.org/article/MED/20976243). The method for calculating the scores remains the same, except that we now only take into consideration MANE transcripts (or where there is no MANE, the best available transcript). These updated DS scores and sampling probabilities have improved predictive power in identifying deleterious CNVs. Please note, the new scores are not comparable with the old scores. All scores displayed on the DECIPHER website have been recalculated. The following example shows the updated scores for a deletion on chromosome 7: https://www.deciphergenomics.org/patient/271096/genotype/45676/browser ACMG secondary findings reporting information has been updated to v3.1 (https://europepmc.org/article/MED/35802134). This version includes the addition of five genes, including four associated with cardiomyopathy (BAG3, DES, RBM20, TNNC1). This information is displayed on the clinical tab on gene pages, patient variant gene tabs and genes tables. Updated information can be viewed for RBM20 here: https://www.deciphergenomics.org/gene/RBM20/overview/clinical-info The order of gene/disease association resources has been updated on the clinical tab on gene pages. Gene2Phenotype (https://www.ebi.ac.uk/gene2phenotype) gene/disease associations are now displayed at the top of the page. This change can be viewed for MYBPC3 here: https://www.deciphergenomics.org/gene/MYBPC3/overview/clinical-info Update to DECIPHER's consent and assent forms - transition to EBI ============= DECIPHER has been awarded a Wellcome grant to continue its work through to 2025. The grant provides for a transition of DECIPHER's hosting and development from the Wellcome Sanger Institute to the European Bioinformatics Institute (EMBL-EBI; https://www.ebi.ac.uk), which runs Ensembl and its Variant Effect Predictor (VEP), Gene2Phenotype and many other resources which are critical to DECIPHER's work. The DECIPHER consent and assent forms, which provide consent for sharing patient data openly on the DECIPHER website, have been updated to reflect this transition and EMBL-EBI is now listed at the bottom of the forms. The assent form has also been reviewed to ensure consistency with the consent form. The updated consent (v8, 2022) and assent forms (v7, 2022) can be downloaded from the following page: https://www.deciphergenomics.org/about/downloads/documents. Please use the update versions going forward. In relation to the transition to EMBL-EBI, Co-PI Helen Firth will remain the clinical lead; Matt Hurles will step back as co-PI but will remain involved as a collaborator and Fiona Cunningham, who leads EBI's Genome Interpretation Team, will join as co-PI. Both institutes are committed to a smooth transition and the migration will not involve any changes to the address (URL), the appearance, or the functionality of DECIPHER. The Deciphering Developmental Disorders (DDD) project (https://www.ddduk.org), which has recruited nearly 14,000 families in the UK and Ireland, will still deliver results through DECIPHER, while the research work will remain at Sanger. Inactive DECIPHER Accounts ============= It is important that DECIPHER accounts are linked only to individuals who are currently actively working in research or clinical genetics and affiliated with their projects' lists. We will soon be locking a number of DECIPHER accounts which no longer appear to be in use to minimise the risk of unauthorised access. If you last logged into DECIPHER prior to 1 September 2020, please make sure you log in again using your email address and password, if you want to retain your access to DECIPHER. We're very grateful for the coordinators who monitor their project's lists on an ongoing basis. ============= We look forward to your feedback and suggestions for improvement. Please use the "Feedback" button which is available on every page and fill in the simple form to get in touch with us. Your details will be filled in automatically if you are logged in. Best Regards Julia, on behalf of the DECIPHER team Julia Foreman PhD DECIPHER Project Manager Email: contact@deciphergenomics.org<mailto:contact@deciphergenomics.org> Web: https://www.deciphergenomics.org Twitter: @decipher_wtsi