Training activity information
Details
Annotate genomic variation data in the context of inherited and acquired disease
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.
Considerations
- Importance of transcript selection
- Quality and consistency of the data and external sources of information
- Sources for annotation e.g., population databases, splicing prediction tools, in silico prediction tools and critically evaluate their suitability
- HGVS nomenclature
- Storage of data in appropriate formats according to local and national standards, taking into consideration patient confidentiality
- Best practice guidelines
- Implications for the patient
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 is the goal of accurately annotating genomic variation data for both inherited and acquired diseases? What specific databases and tools are expected for annotation, what level of detail is required, and how does the context (inherited vs. acquired disease) influence the annotation process?
- Are you familiar with variant call format (VCF) files and public databases for variant annotation (e.g., dbSNP, ClinVar, COSMIC)? What possible challenges might you face, e.g. navigating complex databases, integrating information from multiple sources, understanding different annotation scores, or annotating rare or novel variants? How might you handle these challenges? When would you need to seek advice if you are unsure about interpreting conflicting annotation results or if a variant’s significance is unclear? How do you feel about annotating genomic variation data?
- What specific skills do you want to develop e.g. such as becoming more proficient in a particular annotation pipeline or database? Improving your ability to assess the reliability of different annotation sources? What specific insights do you hope to gain into how annotation databases are structured, the types of information they provide, and how annotation differs between inherited and acquired disease contexts?
- If you’ve annotated variants before, have you reviewed any notes on difficulties encountered or areas for improvement in your approach? What important information do you need to consider before embarking on the activity, e.g. ensuring access to necessary annotation tools and databases, understanding specific dataset requirements (e.g., filtering criteria, variant types), and reviewing relevant literature or guidelines on variant annotation?
In action
- As you are annotating genomic variation data, make a note of anything that feels surprising or different from what you anticipate. For example, does a specific variant return conflicting information from different databases, do you encounter novel variants with no prior annotation, or does the annotation tool behave unexpectedly? Consider how this experience compares with previous experiences of similar activities, such as general data annotation or database interaction. Does it feel more or less familiar, particularly regarding the nuances of inherited vs. acquired disease contexts?
- Identify how any unexpected developments, such as conflicting annotation results or a tool error, impact your immediate actions. Do you immediately cross-reference with another database, consult the tool’s documentation, or pause to consider the implications of conflicting data? Do you adapt or change your annotation approach or strategy as a result? For instance, do you prioritise certain databases over others, or do you adjust your filtering criteria on the fly? Do you find it difficult to adapt to ambiguous or conflicting information? Does it affect your confidence in your ability to interpret annotation results accurately? Do you feel positive you can reach a successful conclusion?
- Do you recognise when you might need to seek immediate advice or help, such as when a variant’s significance is unclear even after extensive searching or when dealing with highly specialised disease contexts you are unfamiliar with? Identify what you learn as a result of the unexpected development. For instance, do you learn a new strategy for reconciling conflicting database entries, a specific characteristic of annotation in acquired vs. inherited diseases, or a more efficient way to navigate a particular annotation tool?
On action
- Summarise the key steps involved in annotating the genomic variation data. Describe the dataset you worked with and the specific tools or databases you used for annotation, noting how you considered the context of inherited and acquired disease. Were there any specific events, actions, or interactions that felt important during the annotation process?
- What specific learning can you take from this annotation task? For example, what strengths did you demonstrate in using annotation tools or integrating information? What skills or knowledge gaps were evident regarding specific databases or applying the context of inherited/acquired disease? How did this experience compare against previous times you have annotated variant data? Were any previous actions for development in this area achieved? Do you feel your practice has improved? Identify any challenges you experienced, such as conflicting information between databases, dealing with novel variants, or understanding disease implications, and how you reacted to them. Did these challenges affect your ability to deal with the situation? Were you able to overcome them? Was there anything significant about this activity, such as needing to seek advice or clarification on interpreting annotation fields or understanding the disease context?
- Identify the specific actions or ‘next steps’ you will take based on this experience to support your learning. What will you do differently next time you annotate genomic variation data? Has anything changed in terms of what you would do if faced with a similar situation again? Do you need to practice using specific annotation databases, integrating information from multiple sources, or applying disease context further?
Beyond action
- Consider the different times you have performed variant annotation for inherited or acquired disease cases. Have you revisited your reflections on challenging or unusual annotations? What specific actions did you previously plan to improve your annotation process, such as exploring new databases, refining filtering steps, or improving documentation? Have you successfully integrated these actions into your annotation workflow? Are you consistently applying improved annotation techniques and utilising resources more effectively based on your cumulative experience? Has discussing complex annotations or the use of specific annotation tools with peers provided new insights that have changed your approach?
- How has repeated practice in annotating diverse genomic variation data across different inherited and acquired disease contexts developed your capability? Do you now more efficiently navigate annotation resources or identify relevant information? How does the cumulative learning from annotating variants prepare you for assessments like annotating a variant, presenting variant interpretation, or discussing variant effects? Do your experiences help you determine when an annotation task might require expert review or be outside your current scope, especially for rare or complex variants?
Relevant learning outcomes
| # | Outcome |
|---|---|
| # 1 |
Outcome
Explain the structure of the human genome and the impact of variation on human development, health, and disease. |
| # 2 |
Outcome
Evaluate sources of information about variation in the human genome including access, application and clinical impact. |
| # 3 |
Outcome
Select appropriate tools for next generation sequencing (NGS) analysis of inherited and acquired disease. |
| # 4 |
Outcome
Analyse NGS data in a clinical setting applying appropriate quality control and data validation. |