Dear All,

Greetings from sunny, chilly, autumnal East Anglia.

In this update:

· Wellcome funding and move to EBI

· DECIPHER v11.8 Released

o New sequence variant and protein pages

o Clinvar annotation tab

o Deposition of mosaicism by tissue, for mosaic UPD variants

· Optional DECIPHER ClinVar submission

Wellcome funding and move to EBI

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We are pleased to announce that 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 17 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. It is intended that the team will move in April 2022. 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 expect to provide further information on the arrangements to DECIPHER depositors closer to the time of the move.

DECIPHER v11.8 Released 

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You can also view this on the web at: https://www.deciphergenomics.org/about/news

It is now possible to search for information about single sequence and protein variants. DNA sequence variant search supports searching by GRCh38 location, by SPDI, HGVSg or Ensembl stable IDs, in addition to HGVSc plus HGNC gene symbol or Refseq transcript. Protein variant search supports searching by HGVSp (single letter or trigraph) plus HGNC gene symbol of Refseq transcript. Searching for sequence variants now takes you to a dedicated sequence variant page, which displays information relevant to that variant. The following page provides information on a missense variant in SPOP: https://www.deciphergenomics.org/sequence-variant/17-49619031-C-T/patient-overlap/identical. Searching for protein variants takes you to a dedicated protein variant page, which displays information relevant to that protein change. The following page provides information on a Arginine to Tryptophan change in PACS1: https://www.deciphergenomics.org/protein-variant/ENSG00000175115-203-R-W/protein

A new Clinvar annotation tab is available on patient variant, sequence variant and protein variant pages. This tab contains information about ClinVar assertions. In this example, the variant has 0, 1 and 2 star ClinVar assertions: https://www.deciphergenomics.org/protein-variant/ENSG00000175115-203-R-W/annotation/clinvar

It is now possible for depositors to record mosaicism by tissue, for mosaic UPD variants.

Optional DECIPHER ClinVar submission

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DECIPHER now supports the deposition of variant data to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar) to enable the greater sharing and aggregation of variant data globally. Submission is optional and the coordinator(s) of a DECIPHER project must approve ClinVar deposition before DECIPHER will deposit data to ClinVar on their behalf.

DECIPHER will only deposit variant data from openly shared patient records, for which explicit patient consent for open sharing has been recorded in DECIPHER. Only openly shared data will be included in the submission. DECIPHER will deposit variant information and high level phenotype information, in addition to a link to the relevant DECIPHER patient record.

If you are interested in DECIPHER submitting the openly consented data in your project to ClinVar, please speak with the coordinator(s) of the project at your centre and/or contact us at contact@deciphergenomics.org

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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

Web: https://www.deciphergenomics.org

Twitter: @decipher_wtsi