Dear All,

Greetings from a sunny East Anglia where spring is finally here.

In this update:

- DECIPHER v11.2 Released

o Interpreting CNVs according to ACMG/ClinGen technical standards

o Developments for variant interpretation

o Further support for centres still working in GRCh37

o Genome Browser Improvements

- Upcoming domain change - https://deciphergenomics.org

- Change to bulk upload template

DECIPHER v11.2 Released 

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You can also view this on the web at: https://decipher.sanger.ac.uk/about/news

Interpreting CNVs according to ACMG/ClinGen technical standards

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It is now possible for depositors to record the evidence used to classify copy-number variants according to the ACMG/ClinGen technical standards for the interpretation of CNVs (https://pubmed.ncbi.nlm.nih.gov/31690835/). To access this interface, select the variant for interpretation on the genotype tab and click on the “Pathogenicity evidence” tab at the bottom of the page.

Bulk upload has also been updated to allow users to bulk deposit CNV pathogenicity evidence.

Developments for variant interpretation

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Gene pages and protein browsers now have a link to Missense3D-DB (http://missense3d.bc.ic.ac.uk:8080), an atom-based analysis and repository of 4M human protein-coding genetic variants. The following page shows these links from the SCN2A gene page: https://decipher.sanger.ac.uk/gene/SCN2A/overview/protein-genomic-info. There is a link listed under “Search databases” and a further link is display by clicking on the “Links” button above the protein browser. A paper describing Missense3D-DB is available: https://pubmed.ncbi.nlm.nih.gov/33502607/.

Gene pages, tables of genes, and the genome browser now indicate the inheritance of disorders reported in OMIM. The following link shows the EP300 gene page with OMIM inheritance terms displayed: https://decipher.sanger.ac.uk/gene/EP300/overview/clinical-info

Tables of genes now also contain links to the Gene Curation Coalition (GenCC) Database (DB). The GenCC-DB provides information pertaining to the validity of gene-disease relationships submitted by GenCC member organizations: https://thegencc.org. The GenCC-DB links for genes within a duplication can be viewed here: https://decipher.sanger.ac.uk/patient/295184/genotype/70682/genes. The GenCC-DB link for each gene is accessed by clicking on the “View” buttons in the “Links” column.

Further support for centres still working in GRCh37

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When a variant has been lifted over from GRCh37 and there are genes overlapping the 37 position which do not overlap the 38 position, we now display a list of these genes in the liftover information window and on the genes tab for patient variants. The following link shows this list of genes on the genes tab (in the blue information box) for a deletion on chromosome 15: https://decipher.sanger.ac.uk/patient/368663/genotype/149094/genes. The liftover information window, which also shows this gene list, can be accessed by clicking on the “?” icon in the genotype table next to the genomic coordinates of the deletion. 

When searching DECIPHER using GRCh37 coordinates, the GRCh38 position is now shown. The following link shows this for a region on chromosome 6: https://decipher.sanger.ac.uk/search/patients/results?q=grch37%3A6%3A157099063-157531913

It is now possible to search in the browser (https://decipher.sanger.ac.uk/browser) using GRCh37 coordinates, by prefixing the coordinates with “grch37:”; these coordinates will be lifted over to GRCh38 before performing the search.

Genome Browser Improvements

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The genome browser now labels MANE Select transcripts. The order in which transcripts are drawn has been adjusted slightly, in so that MANE Select transcripts are usually the topmost transcript drawn in a gene. MANE Select transcripts are a single high-quality transcript for a gene that is well-supported by experimental data and represents the biology of the gene. Further information about the MANE project can be found here: https://www.ncbi.nlm.nih.gov/refseq/MANE

To assist users in knowing which filters are applied in the genome browser, the genome browser now indicates beneath the track label when filters and certain colour schemes are applied.

The genome browser now displays genes in the Gene track which do not have dosage sensitivity predictive scores differently depending on whether or not they are protein coding. Non-coding genes appear in grey while coding genes remain black.

Upcoming domain change - https://deciphergenomics.org

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The DECIPHER URL (the address you see at the top of your web browser) will soon be changing from: https://decipher.sanger.ac.uk/ to: https://deciphergenomics.org/ – in fact you can use the new URL right away – it will simply redirect you.

Even though DECIPHER contributors come from across the globe, we sometimes get feedback that we are a UK-specific resource: we don’t want our URL to misleadingly reinforce that perspective.

When we change over, everything else will remain the same – the same servers will be hosting the same site. The only thing you might notice is that you might be prompted to log in again, if you happen to be logged in during the changeover.

All links to the current domain will redirect and we are particularly aware of the need to maintain continuity for links of the form https://decipher.sanger.ac.uk/patient/283351 – which are used regularly in papers and in services like the Ensembl browser which display DECIPHER patient data. You will also notice changes to our email addresses – our main address will change to contact@deciphergenomics.org.

Change to bulk upload template

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The bulk upload template for sequence variants and CNVs have changed to reflect the addition of CNV pathogenicity evidence. If the depositors are providing pathogenicity evidence criteria, the evidence framework used must now be specified.

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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: decipher@sanger.ac.uk

Web: https://decipher.sanger.ac.uk

Twitter: @decipher_wtsi