19.07.19 Guidelines for WES/WGS

Question 1

Benefits of WES over WGS

Answer 1

• only sequencing 1% of genome but identify 85% of pathogenic variants
• Less data generated
• Cheaper

Question 2

Benefits of WGS over WES

Answer 2

• remaining 99% of genome covered
• overall better calling of structural variants
• No capture-based bias

Question 3

Current ACMG guidelines of when WES/WGS should be used

Answer 3

• Family history suggestive of mendelian inheritance. Phenotype doesn’t fit with a known syndrome for which targeted testing is available
• For conditions with a high degree of genetic heterogeneity
• Targeted testing has not identified a pathogenic variant

Question 4

Current ACMG guidelines of when WES/WGS should NOT be used

Answer 4

• Prenatal/ new born testing

- Preferable to do a first line targeted approach (also reduces likelihood of IFs)

Question 5

Pre-test considerations

Answer 5

• Patients are informed of likely outcomes and possibility of incidental findings.
• Appropriate consent should be obtained (will data be used by research?). Option to not receive IFs.
• Reporting lab should report the sensitivity/specificity reportable range for their test. Have a policy regarding reporting of IFs

Question 6

What should be included in report

Answer 6

• patient details and diagnosis
• Limitations of test (horizontal coverage- % of ROI covered, vertical coverage- sensitivity defined by read depth, CNV detection)
• Method of data analysis
• Result validation by alternate method (e.g. Sanger), also confirms sample identity