Dear All,

Greetings from a grey and murky East Anglia.

In this update:

- DECIPHER v11.9 Released

o Regulatory features genome browser track

o AlphaFold predicted 3D protein structures

o neXtProt functional annotations

o MANE Plus Clinical transcripts

o Links to IEMbase

o ClinGen Expert Panel Interpretations

o ClinGen SVI recommendations for population data

o Protein browser

§ Conservation track

§ Number of transcripts sharing each exon

o Grantham distance scores

DECIPHER v11.9 Released 

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

A regulatory features track in now displayed in the genome browser which displays features from the Ensembl Regulatory Build, which are predicted to regulate gene expression. This will particularly assist the interpretation of variants in the non-coding genome.

AlphaFold predicted 3D protein structures can now be accessed through the protein browser. AlphaFold was first published in July and DECIPHER users can now view a patient’s variant on the predicted structure to improve interpretation in the clinic. The AlphaFold predicted structure for EP300 can be viewed here: https://www.deciphergenomics.org/gene/EP300/overview/protein-genomic-info

Manual annotations that capture the phenotypic effect of genetic variations from the neXtProt knowledgebase are now displayed on a functional annotation tab. This includes functional annotation for variants in 130 clinically important genes, including ion channels, protein kinases and cancer genes. Functional annotation for MSH2 p.Gly322Asp can be viewed here: https://www.deciphergenomics.org/protein-variant/ENSG00000095002-322-G-D/annotation/functional

MANE Plus Clinical transcript annotations are now displayed in DECIPHER. These transcripts are additional transcripts per locus (to the MANE Select transcript) necessary to support clinical variant reporting, e.g. which contain known pathogenic variants. MANE Plus Clinical transcripts are displayed in the genome browser and in the variant deposition form.

Links to IEMbase, an online expert-curated inborn errors of metabolism (IEM) knowledge base are now provided on gene pages. Links for GRIN1 can be seen for here under the Management resources section: https://www.deciphergenomics.org/gene/GRIN1/overview/clinical-info

ClinGen Expert Panel Interpretations are now displayed on ClinVar/ClinGen annotation tabs (https://www.deciphergenomics.org/sequence-variant/18-55228323-TTC-T/annotation/clinvar). In addition, ClinGen SVI recommendations regarding the use of population data when interpreting sequence variants, are also now displayed in the pathogenicity evidence interface. ClinGen SVI recommend BS1 and BA1 can be met by population databases, whilst BS2 can only be met when you have a well phenotyped individual known to be without the disease.

A conservation track displaying the protein sequence of orthologous genes is now available on the protein browser. In addition, the number of transcripts sharing each exon in displayed, which can be important when interpreting single-exon deletions. These new features can be viewed for EP300 here: https://www.deciphergenomics.org/gene/EP300/overview/protein-genomic-info

Grantham distance scores, which predict the effect of substitutions between amino acids based on chemical properties, are displayed on the VEP consequence tab.  Grantham distance scores for a Tyrosine to Phenylalanine substitution can displayed here: https://www.deciphergenomics.org/patient/293944/genotype/200339/annotation/vep-prediction

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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.

Festive Wishes

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