[Decipher-announce] DECIPHER May 2022 Update

Dear All, Greetings from a sunny and warm East Anglia. In this update: - DECIPHER v11.12 Released o New Cardiac Features § Variant Disease Cohort Allele Frequencies § Gene2Phenotype Gene/Disease Assertions o Update to de novo Inheritance Terms - Inactive DECIPHER Accounts - Wellcome Funding and Move to EBI DECIPHER v11.12 Released ============= You can also view this on the web at: https://www.deciphergenomics.org/about/news DECIPHER now displays cardiac variant allele frequencies. This data indicates if a variant has been observed in hypertrophic cardiomyopathy, dilated cardiomyopathy, or in healthy volunteers. This data will assist in variant interpretation and make it easier to know when to apply the ACMG/AMP sequence variant PS4 criterion during a variant pathogenicity assessment. Cohort ethnicity and age distributions are provided where available. The allele frequencies can be viewed on the "Annotation" tab on patient records, variant pages or protein variant pages under "Disease cohort" for the cardiac genes, where this is available. The following page displays hypertrophic cardiomyopathy cohort data for a variant in MYBPC3: https://www.deciphergenomics.org/protein-variant/ENSG00000134571-502-R-W/an… Cardiac Gene2Phenotype gene/disease assertions are now displayed on gene pages and in gene tables, assisting with interpretation of variants in genes associated with cardiac disease. As with other Gene2Phenotype assertions, further information such as the mutation consequence can be viewed by clicking on the gene/disease assertion. Cardiac Gene2Phenotype gene/disease assertions for MYH7 can be viewed here: https://www.deciphergenomics.org/gene/MYH7/overview/clinical-info These cardiac features complement the cardiac control cohort information, which provide quantitative estimates that a rare variant in a gene is causative of a disease, and cardiac mutational hot spots data that were released in April. The "de novo" inheritance option has now been replaced with "de novo (parentage confirmed)" and "de novo (unconfirmed parentage)". This allows depositors to record confirmed parental relationships versus assumed parental relationships status for de novo variants, which is important when determining the strength given to case level data during a variant pathogenicity assessment, specifically for ACMG/AMP sequence variant criteria PS2 and PM6. Variants deposited prior to this release will be marked as unconfirmed, except for where depositing centres have let us know that the variants they have deposited are confirmed. If the de novo variants from your centre should be displayed as "de novo (parentage confirmed)", rather than "de novo (unconfirmed parentage)", please email contact@deciphergenomics.org<mailto:contact@deciphergenomics.org> and provide details. Please note that this change affects users depositing via bulk upload. Inactive DECIPHER Accounts ============= It is important that DECIPHER accounts are linked only to individuals who are currently actively working in research or clinical genetics. We will soon be identifying and 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 17th June 2020, please make sure you log in again using your email address and password, if you want to retain your access to DECIPHER. After 17th June 2022, we intend to lock accounts which have not been accessed in the previous two years. If your account is locked, you will need to reset your password before you can regain access. We're very grateful for the coordinators who monitor their project's lists on an ongoing basis. Wellcome Funding and Move to EBI ============= DECIPHER has been awarded a new Wellcome grant to continue its work through to 2025. Key goals include better support for variants in the non-coding genome, helping users find relevant functional evidence, and building models to link genes and disorders with phenotypes. The grant will allow us to keep DECIPHER up to date with best practice and emerging opportunities in clinical interpretation as the landscape evolves. The grant also provides for a transition of DECIPHER's hosting and development from the Wellcome Sanger Institute (where DECIPHER began and has been based for the last 18 years) 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. 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. ============= 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