Training activity information
Details
Analyse and interpret the results of NGS for a panel of genes related to adult-onset disorders
Type
Entrustable training activity (ETA)
Evidence requirements
Evidence the activity has been undertaken by the trainee repeatedly, consistently, and effectively over time, in a range of situations. This may include occasions where the trainee has not successfully achieved the outcome of the activity themselves. For example, because it was not appropriate to undertake the task in the circumstances or the trainees recognised their own limitations and sought help or advice to ensure the activity reached an appropriate conclusion.
Reflection at multiple timepoints on the trainee learning journey for this activity.
Reflective practice guidance
The guidance below is provided to support reflection at different time points, providing you with questions to aid you to reflect for this training activity. They are provided for guidance and should not be considered as a mandatory checklist. Trainees should not be expected to provide answers to each of the guidance questions listed.
Before action
What does success look like?
- Identify what is expected of you in relation to analysing and interpreting NGS panel results for adult-onset conditions.
- Review the relevant learning outcomes, specifically concerning the interpretation of genomic variants and the interpreting and reporting of genomic testing relevant to adult-onset disorders.
- Discuss with your training officer what constitutes a thorough and accurate analysis and interpretation of NGS panel data, including the expected level of detail in identifying and classifying variants.
What is your prior experience of this activity?
- Think about what you already know about analysing and interpreting NGS data or panel testing.
- Consider possible challenges you might face, such as dealing with large datasets from a gene panel, interpreting variants of uncertain significance (VUS), or correlating genomic findings with adult-onset phenotypes. How might you handle these?
- Recognise the scope of your own practice, knowing when you will need to seek advice or help with complex interpretations, and from whom.
- Acknowledge how you feel about embarking on the analysis and interpretation of complex NGS panel data.
What do you anticipate you will learn from the experience?
- Consider the specific skills you want to develop, drawing upon previous experiences (if any). This could include refining your variant filtering strategies or improving your ability to assess the clinical significance of variants.
- Identify the specific insights you hope to gain, such as a deeper understanding of the spectrum of genetic variants identified by panels or the challenges of interpreting variants with age-dependent penetrance.
What additional considerations do you need to make?
- Consult any actions you identified following previous experiences, perhaps from prior variant interpretation activities.
- Identify important information you need to consider before embarking on the activity, such as reviewing guidelines for variant interpretation, familiarising yourself with the specific gene panel being used, or understanding the clinical information provided with the referral.
In action
Is anything unexpected occurring?
- Are you noticing anything surprising or different from what you anticipate during the NGS data analysis and interpretation?
- Are you encountering situations such as:
- The identification of a novel variant with contradictory bioinformatic predictions (e.g., conflicting scores from different variant calling algorithms)?
- Persistent issues when integrating data from different variant calling algorithms, making it difficult to establish the presence or quality of a variant?
- Encountering a Variant of Uncertain Significance (VUS) that is difficult to dismiss yet does not immediately correlate with the patient’s adult-onset phenotype?
- How is this experience comparing with previous experiences of similar activities?
How are you reacting to the unexpected development?
- How is this impacting your actions? Did you adapt or change your approach to filtering or analysis in the moment?
- Consider the steps you are taking in the moment, such as:
- Immediately checking additional variant databases or consulting interpretation guidelines to investigate unexpected or unclear genetic findings.
- Employing alternative analysis strategies to confirm the presence or classification of a complex mutational profile.
- Seeking immediate advice from a senior colleague or a clinical scientist regarding the interpretation of a novel or complex variant found on the panel.
- How are you feeling in that moment? Is the unexpected finding affecting your confidence in the diagnostic sequence you are following? Are you finding it difficult to adapt your knowledge of clinical significance to the observed patterns of genetic alterations? Do you feel positive you can reach a successful conclusion?
What is the conclusion or outcome?
- Identify how you are working within your scope of practice when interpreting the data e.g., ensuring your analysis accurately documents data reliability limitations and classification rationale.
- What are you learning as a result of the unexpected development? For example, are you mastering a new troubleshooting technique for integrating data from different bioinformatic tools, or gaining crucial insight into the clinical relevance of VUS findings for specific adult-onset disorders?
On action
What happened?
- Begin by summarising the key points of the experience, detailing the key genetic findings (e.g., sequence variants) you identified in the NGS results.
- Describe how the results, including variants of uncertain significance (VUS) or complex findings, related to the patient’s adult-onset phenotype.
- Describe any unexpected or complex findings that required careful analysis and interpretation.
- Reflect on any specific feelings or challenges experienced during the analysis and interpretation process, and include any ‘reflect-in-action’ moments where you adapted your analysis plan.
How has this experience contributed to your developing practice?
- Identify what learning you can take from this experience. What skills or knowledge did you develop or improve in analysing and interpreting NGS data for adult-onset disorders? What learning specifically relates to the bioinformatic tools or best practice guidelines used for interpretation?
- How did this experience compare to previous times you have analysed NGS data? Has your practice improved?
- Consider whether you were able to work appropriately within your scope of practice during the analysis and interpretation, for instance, by knowing when to escalate a complex VUS for senior review.
- What strengths did you demonstrate, or what skills and/or knowledge gaps were evident?
What will you take from the experience moving forward?
- Identify the actions or ‘next steps’ you will now take to support the assimilation of what you have learned, including incorporating any feedback received about your ability to accurately analyse and interpret the results..
- How will you ensure accuracy and consistency in your analysis and interpretation of NGS data in the future, for example, by refining your variant filtering strategy?
- What areas for continued development have been identified in your ability to analyse and interpret NGS results for adult conditions? Do you need to practise any aspect further?
Beyond action
Have you revisited the experiences?
- Revisit the NGS analysis and interpretation you performed for this activity. Evaluate and re-evaluate the steps you took and the conclusions you reached, particularly regarding variant classification.
- Compare your current analytical approach to interpreting NGS data with how you initially approached it. How have your skills developed (e.g., refining VUS management)?
- Have you encountered more complex NGS datasets or challenging variants since, which have refined your analytical skills beyond what you initially learned? Have you completed the actions identified in previous reflections to improve your analysis and interpretation practice?
How have these experiences impacted upon current practice?
- How do you apply the analytical and interpretation skills developed through this activity to interpreting other types of genetic results or datasets in your current work (e.g., targeted sequencing, whole exome data)?
- How has gaining more experience in interpreting genomic variants influenced your confidence and accuracy in this task?
- Have any specific challenges encountered during this activity or subsequent experiences highlighted the importance of using bioinformatic tools and best practice guidelines for variant classification?
- How does the accumulated learning from this activity support your preparation for observed ‘in-person’ assessments, such as a DOPS titled ‘Classify a variant’?
- Considering the increasing complexity of genomic data from NGS, how will your foundational analytical and interpretation skills help you to interpret and integrate new types of information in the future?
- What actions will you take to continue developing your bioinformatic skills and stay current with interpretation guidelines (e.g., attending national variant meetings)?
Relevant learning outcomes
| # | Outcome |
|---|---|
| # 2 |
Outcome
Perform molecular analysis for patients referred with adult-onset disorders. |
| # 4 |
Outcome
Interpret genomic variants, including copy number and structural changes and investigate the clinical significance of variants using bioinformatic tools using best practice guidelines. |