Whole Genome Sequencing - Rare Disease C&S GLH

The implementation of Whole Genome Sequencing (WGS) for Rare Disease as a routine diagnostic service is being carried out through distinct phases, with clinical indications from the National Genomic Test Directory eligible for WGS as part of these phases. We are currently in phase 2. WGS testing is only available for patients in England. Testing for devolved nations patients is available for some indications via Exome sequencing.

Please note that WGS testing will only begin and samples will only be sent for sequencing once all forms have been completed with all of the required information and samples have been received. The omission of any information will result in a delay to sample submission. The laboratory will need to contact you to request any missing information, please avoid sending incomplete documentation.

The regional Clinical Genetics departments and Central and South Genomic Medicine Service Alliance (GMSA) are also developing a network of genomic practitioners and genomic associates who can undertake some of the administrative tasks associated with WGS requesting e.g. patient consent. Please contact your local Clinical Genetics service if you require further information about the availability of this support.

Please see the National Genomic Test Directory for Rare and Inherited Disease to see which clinical indications are tested for by WGS. This can be found here.

Semi-Rapid testing for clinically urgent patients is available for the following indications, by Exome sequencing. Please see the Rare and inherited disease eligibility criteria document for further information on eligibility.

Clinical Indication and Testing Laboratory
Code Clinical Indication Testing Laboratory
R15 Primary immunodeficiency or monogenic Inflammatory Bowel Disease Great Ormond Street Genetics Laboratory
R98 Likely inborn error of metabolism - targeted testing not possible West Midlands Regional Genetics Laboratory
R135 Paediatric or syndromic cardiomyopathy Oxford Genetics Laboratory
R257 Unexplained young onset end-stage renal disease Bristol Genetics Laboratory

Urgent testing for children in NICU/PICU should be via the R14 Rapid Clinical Genome indication where appropriate and following discussion with Clinical Genetics.

Please note that if additional panels are selected for testing on the WGS test order form then the laboratory that provides testing for the main clinical indication selected on the form will also analyse these panels.

Guide and FAQ document

A guide and frequently asked questions document for the Genomic Medicine Service and Whole Genome Sequencing can be found here

This document contains helpful information on the Genomic Medicine Service, how to use PanelApp, and how to request testing and complete forms for Whole Genome Sequencing. If you have a query regarding Whole Genome Sequencing, please check whether your question is present within the frequently asked questions section before contacting the laboratory.

How to order a Whole Genome sequencing test

In brief, in order to request a WGS test for your patient you will need to complete the following steps:

Step 1 - Check patient eligibility

Eligibility criteria for rare diseases can be found in the rare and inherited disease eligibility criteria document for the Genomic Medicine Service here.

If you need to query whether you can request WGS for your patient then please contact bwc.centralsouthglh@nhs.net.

Step 2 - Collect patient samples

Blood samples in EDTA are required in order to extract DNA for Whole Genome Sequencing. This should be at least 1-3 mL for neonates and 3-5 mL for other patients referred. Blood samples should be sent to your local genetics laboratory and will be forwarded on to the West Midlands Regional Genetics Laboratory for DNA extraction and sending for Whole Genome Sequencing. Samples can either be sent with the Whole Genome Sequencing test order form (see below), or with a standard genomics referral form with WGS noted on the form (and the Whole Genome Sequencing test order form and Record of Discussion form sent by e-mail).

For the majority of clinical indications currently being tested, it is highly recommended that a trio is referred for testing (proband and biological parents), however, it is acceptable to refer a duo (proband and one biological parent) or singleton where one or more parents are not available. It is recognised that for some patients, with an adult-onset disorder, parental samples will not be available and singleton testing will be required.

It is possible for a stored DNA sample to be used for Whole Genome Sequencing, but the sample must have been extracted in a UKAS-accredited laboratory and will be required to pass all quality control checks. Please contact your local laboratory if you think that there is stored DNA available for testing. However, a fresh blood sample is preferred if possible.

If the DNA extracted from a blood sample you have sent from a patient, or from stored DNA, does not pass the quality control checks required then you will be notified of this and the requirement for a new blood sample to be sent.

Step 3 - Complete Test Order form and Record of Discussion form

Whole Genome Sequencing requires:

  • a blood sample for each family member to be tested
  • a Test Order form for family – download here  
  • a Record of Discussion form for each family member recruited – download here
  • If more than two family members are being recruited there is a form to be completed to add additional family members – download here 

All forms are editable PDFs and should be e-mailed to bwc.centralsouthGLH@nhs.net when completed. Please see the NFAW/Guide document for further information on how to complete the Test Order and Record of Discussion forms. All forms should be completed in full with all pages of the forms completed. These forms should not be used for non-Whole Genome Sequencing testing. Where possible, forms should be completed electronically to enable them to be processed accurately.

Where a patient is not able to complete a Record of Discussion form (deceased/lacks capacity) then a Consultee Declaration form can be completed by a consultee of the patient – download here 

If required, a young person assent form is available for clinicians to utilise – download here

If a patient wishes to withdraw consent for their data to be available in the Research Library, the following form should be completed and returned to the laboratory – download here

If patient wishes to opt-in for their data to be available in the Research Library, if they had previously not provided consent for this, then the following form should be completed and returned to the laboratory – download here

A note on penetrance setting selection

The penetrance selected on the test order form has a direct impact on the variants in the patient that pass the filtering performed by the bioinformatics pipeline. Where complete penetrance is selected, and family members referred for testing are entered as unaffected, variants present in both the patient and in family members will be filtered out and not analysed (for variants in genes with autosomal dominant or some X-linked mode-of-inheritance). If a family member is referred for testing and entered as affected then only variants which are present in affected members of the family will pass the filtering and be analysed. If incomplete penetrance is selected then variants in unaffected family members referred, and inherited by the patient, will not be filtered out. Incomplete penetrance should be selected when; parent may be mildly affected but has not been entered on test order form as affected, or when a patient is suspected of having a disorder which can present with incomplete penetrance. If a penetrance is not selected on the test order form then a default penetrance will be selected.

Please note that penetrance is selected at the patient level and not the panel level.

Therefore the default penetrance selected will be based on the main test order code selected and not those of any additional panels. If you wish to discuss the appropriate penetrance setting for a patient before completing the test order form, please either contact the laboratory or your local clinical genetics laboratory.

Please see penetrance pedigree examples here for some helpful examples of what penetrance selection means in practice.

Turnaround times

Please note that all turnaround times do not begin until all samples and completed forms have been received. The omission of any information will result in a delay to sample submission. The laboratory will need to contact you to request any missing information, please avoid sending incomplete documentation.

There is currently a 6-week turnaround time for Whole Genome Sequencing data to be received back from Illumina/Genomics England once samples have been sent. There is then a 6-week turnaround time for the reporting laboratory to analyse and report the results to the referring clinician. Results should therefore be received within 12 weeks of receipt of a complete referral. Please note that this is an indicative turnaround time while the pathways for WGS are being fully established. Please note that turnaround times are currently longer than expected, and patients should be counselled that results are likely to take longer than 12 weeks.


Reanalysis of WGS sequencing data is available, however, we highly recommend that the initial request is complete so please consider all panels which may be appropriate prior to sending Test Order Form. Reanalysis of a new gene panel or applying the latest version of the previous panel is only available where there is a change in clinical circumstances to justify the test.  This would include a significant change in the patient’s disorder, potential new treatment or clinical management applicable or a new pregnancy which might be impacted by testing.  There also needs to be a significant expectation that the re-analysis will provide a diagnosis which was not made by the original test.

For cases that satisfy those requirements, please complete the request form - download here and send it to: bwc.centralsouthGLH@nhs.net