Add and show gene annotation
Background
Note: This issue is dependent on #150 (support for gene annotation)
When evaluating large gene panels with uncertain gene-phenotype relationships, or structural variants (see &2), information relating the function of the gene is important both for locating relevant variants and for making informed decisions about any disease-related consequences of variants in the gene. It can also be important for filtering and ACMG rules, as well as future variant prioritization algorithms.
Note also related issue #17 (gene level references).
Also related to: LA-578; original user request: MEET-156
Implementation
Add annotation sources
Note: Some of the sources could be added as generic links (see #88 (closed)) as a quick fix, but to be available to filter/sort/prioritization it needs to be implemented as actual annotation.
Contenders:
- Gene dosage (originally from #21 (closed))
- Haploinsufficiency and triplosensitive scores from ClinGen Dosage Sensitivity Map. Top level with more curation information: https://search.clinicalgenome.org/kb/curations/, source files appears to be available here: https://ftp.clinicalgenome.org/ - see also #88 (closed)
- Should be displayed at all times, next to gene name (suggestion from MEET-156)?
- Link to particular gene: uses HGNC ID, e.g. [https://search.clinicalgenome.org/kb/genes/HGNC:1100]
- Annotation could be used in PVS1 rule (#102 (closed))
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OMIM
- Syndromes/diseases
- Genes
- References; from OMIM? Relates to #17
- DDD genes (DDG2P): Curated list of genes reported to be associated with developmental disorders
- Phenotype associations: HPO?
- Imprinted genes: Internal?
- ACMG incidental findings list - see also #88 (closed)
- PanelApp: e.g. [https://panelapp.genomicsengland.co.uk/panels/entities/BRCA1] - see also #88 (closed) (https://panelapp.genomicsengland.co.uk/panels/entities/BRCA1) for BRCA1
- Alternative gene names (from HGNC?)
- HGMD default transcript (important if going with MANE as default source in AMG-2057)
- 3'-end vulnerability / NMD? #22 / #15 (closed)
Display annotation
The annotation should be available for any variant in or overlapping a gene. In addition, gene annotation could be relevant when ordering reanalyses.
When classifying variants, gene annotation could be displayed in the gene information popup (see #20 (closed)), but other places will also likely be(come) relevant, e.g. in the side bar full/quick mode, especially when analysing structural variants. Exactly how will be an iterative process that requires feedback from users.