**7. Conclusions**

*Methods in Molecular Medicine*

**126**

**Considerations**

Gene selection

Gene analysis

Appropriate transcripts

Pseudogenes Evaluated homopolymeric regions

Mutation spectrum—reported deep intronic and/or promoter

region variants

CNV analysis Establish if critical variants are not covered by assay

Virtual panel

Expert reviewed panels

Phenotype-driven

**Table 6.**

*Considerations for gene selection, analysis and virtual panel creation.*

creation

Clinical association

**Resources**

ClinGen GeneReviews

LRG

RefSeq

Pseudogene

PanelApp – Genes and

Entities

Ivády et al. [6] PanelApp—Genes and

Entities

ClinVar Decipher PanelApp

ClinGen

HPO

https://panelapp.genomicsengland.co.uk/

https://www.clinicalgenome.org/data-sharing/clinvar/

https://hpo.jax.org/app/

https://www.ncbi.nlm.nih.gov/clinvar/

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

**Links**

https://clinicalgenome.org/curation-activities/gene-disease-validity/

https://search.clinicalgenome.org/kb/gene-validity

https://www.ncbi.nlm.nih.gov/books/NBK1116/

https://www.lrg-sequence.org/

https://www.ncbi.nlm.nih.gov/refseq/rsg/

http://pseudogene.org/

https://panelapp.genomicsengland.co.uk/panels/

entities/?tag=locus-type-pseudogene

DOI: 10.1186/s12864-018-4544-x

https://panelapp.genomicsengland.co.uk/panels/entities/?

The decision to implement WES in a clinical diagnostic environment is one that must take into account local context, which encompasses clinical complexity, staff resources, equipment resources and bioinformatic expertise. The decisions described here were made based on the above considerations with a view to establishing opportunity, the most important of which was to have a WES pipeline that could scale over time in terms of patients tested and with the potential to be a regional resource.

It should be stressed, however, that a WES pipeline is sandwiched by two critical elements: first, the need to focus on the quality and accurate quantitation of genomic DNA; which dictates the quality of everything that happens downstream, and second, to understand that the identification of DNA variants is technically demanding but the classification of those variants is not currently a fully automated process. The former can sometimes be overlooked, while the latter can be a daunting exercise. It is perhaps the subject of another book chapter to discuss the approaches to variant classification.

### **Conflicts of interest**

The authors declare no conflicts of interest.
