Diagnostic Sequencing —
Training activity: 5

Details

Annotate genomic variation data in the context of inherited and acquired disease

Type

Developmental training activity (DTA)

Evidence requirements

Evidence the activity has been undertaken by the trainee​.

Reflection on the activity at one or more time points after the event including learning from the activity and/or areas of the trainees practice for development.

An action plan to implement learning and/or to address skills or knowledge gaps identified.

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 are the intended outcomes of the training activity?

• How does the goal of accurately annotating genomic variants help you explain the structure of the human genome and the impact of variation on human development, health, and disease?
• In what ways will you evaluate sources of information regarding variation—such as dbSNP, ClinVar, or COSMIC—specifically considering their access, application, and clinical impact?
• What criteria are you using to select the most appropriate annotation tools or pipelines for the specific context of inherited or acquired disease for this dataset?
• How will you demonstrate that you are analysing NGS data in a clinical setting while applying the necessary quality control and data validation to the resulting annotations?
• What specific level of detail is required for this annotation task, and have you identified the appropriate filtering criteria and variant types (e.g., SNVs or structural variants) expected for this dataset?

What do you anticipate you will learn from the experience?

• What specific insights do you hope to gain regarding how different annotation databases are structured and the specific types of information they provide for clinical interpretation?
• Based on what you already know about Variant Call Format (VCF) files, what do you anticipate learning about the nuances of annotating rare or novel variants compared to common polymorphisms?
• How do you expect this activity to improve your ability to assess the reliability of different annotation sources and reconcile conflicting annotation scores or results?
• What do you anticipate learning about how the context of the disease (inherited vs. acquired) fundamentally changes the annotation process and the databases used?

What actions will you take in preparation for the experience?

• Have you discussed the activity with your Training Officer to gain clarity on the expected databases, tools, and the definition of a ‘successful’ annotation for this specific task?
• Have you confirmed you have access to the necessary annotation tools and databases and reviewed relevant Standard Operating Procedures (SOPs) or best practice guidelines?
• What steps have you taken to prepare for potential challenges, such as navigating complex databases, integrating information from multiple sources, or troubleshooting tool errors?
• Have you reviewed your notes from previous annotation attempts to identify past difficulties and ensure you have a plan to address those areas for improvement?
• How do you feel about embarking on this training activity, and can you clearly identify the point at which interpreting a variant’s clinical significance would exceed your current scope of practice, requiring you to seek advice?

In action

What are you doing?

• How are you approaching the annotation of genomic variants for this specific dataset, and why have you chosen this particular pipeline or set of tools to address the inherited or acquired disease context?
• What decisions are you making as you progress, particularly regarding the selection of databases like dbSNP, ClinVar, or COSMIC based on their access, application, and clinical impact?
• Which aspects of the annotation process feel intuitive to you, such as interpreting VCF files, and which require more conscious effort, such as explaining how a specific variation relates to the structure of the human genome?
• How are you ensuring that your current approach integrates appropriate quality control and data validation for a clinical setting?

How are you progressing with the activity?

• How effective are your current actions in producing a detailed and accurate annotation that meets the required clinical thresholds?
• What challenges are you facing in the moment, such as encountering novel variants with no prior annotation, managing conflicting information from different databases, or troubleshooting unexpected behaviour from your annotation tools?
• What are you learning as the activity unfolds about how the impact of variation on human health differs between inherited and acquired contexts?
• How does this specific annotation task connect to your existing skills in clinical data analysis and your ability to validate complex NGS results?

How are you adapting to the situation?

• Are there alternative strategies or filtering criteria you should be considering if you encounter ambiguous data or a tool error?
• What support or guidance might you need in this moment—for example, from a Training Officer or a Genomic Scientist—if a variant’s significance remains unclear after extensive searching?
• Are you working within your scope of practice, and can you identify the exact point at which interpreting a highly specialised disease context or complex variant would require escalation?
• How are you adjusting your strategy if the computational resource requirements or the complexity of integrating multiple data sources exceed your initial expectations?

On action

What did you notice?

• How would you summarise the key steps you took to annotate the genomic variation data, and which specific tools or databases (such as dbSNP, ClinVar, or COSMIC) did you utilise?
• How did the specific context of the disease (inherited vs. acquired) influence the way you approached the annotation process and the level of detail you recorded?
• Did you observe any specific events, actions, or interactions—such as unexpected software behaviour or findings in the VCF file—that felt particularly important during the task?
• Were the input and output formats appropriate for the clinical analysis, and did they allow for efficient quality control and data validation?

What did you learn from the activity?

• What specific knowledge did you gain or improve regarding the structure of the human genome and the biological impact of the variations you annotated?
• How did this experience enhance your ability to evaluate sources of information for genomic variation, specifically in terms of their clinical application and reliability?
• What strengths did you demonstrate in selecting appropriate tools for NGS analysis of this specific inherited or acquired disease, and what gaps in your knowledge of annotation pipelines were revealed?
• In what ways did you successfully analyse NGS data in a clinical setting while applying appropriate quality control measures?
• How did you react to challenges such as conflicting information between databases or novel variants with no prior annotation, and were you able to overcome them?
• How did your reflection-in-action (the decisions you made as the task unfolded) influence the final result?

What will you take from the experience moving forward?

• What areas for continued development have you identified, such as a need to better understand specific annotation scores or disease-specific filtering criteria?
• How can you apply the learning from this activity—specifically regarding information evaluation and tool selection—to your routine clinical practice?
• What clear next steps will you take, such as practicing with different annotation databases or refining your methods for integrating information from multiple sources?
• What additional support or resources (e.g., specialist advice on interpreting rare variants) might you need to further develop your proficiency in this area?
• How has this experience changed what you would do if faced with ambiguous annotation results or complex disease contexts in the future?

Beyond action

Have you revisited the experiences?

• How have you evaluated and re-evaluated your reflections from various instances of annotating variants, particularly cases involving challenging or unusual annotations?
• When comparing these experiences with Observed Training Activities (OTAs), what specific observable behaviours have you successfully assimilated into your routine work?
• Through professional storytelling with peers or colleagues, how has your view of the annotation process changed, and have these discussions provided new insights into using specific annotation tools or reconciling conflicting data?
• Have you reviewed your notes on previous annotation tasks to ensure you are now consistently applying improved techniques to explain the structure of the human genome and the biological impact of identified variations?

How have these experiences impacted upon your current practice?

• How has the accumulation of experiences across diverse datasets developed your ability to efficiently navigate annotation resources and identify relevant clinical information?
• In what ways has your cumulative learning from this activity prepared you for formal assessments, such as presenting variant interpretation findings or discussing the effect of different modes of variation on protein function with a Genomic Scientist?
• How have you applied your developed skills in selecting appropriate NGS tools and analysing data in a clinical setting to other training activities or the generation of integrated reports?
• How do you now integrate your knowledge of filtering criteria and variant types into your daily workflow to ensure high-quality data validation?

How might these experiences contribute towards your future practice?

• What transferable skills have you developed—such as integrating complex information from multiple sources or assessing the reliability of databases—that will support your wider practice as a Clinical Bioinformatician?
• Based on your repeated practice, can you more readily determine when an annotation task is particularly complex and potentially outside your current scope of practice, requiring expert review or escalation?
• What clear actions for continued development have you identified, such as exploring new databases or refining your filtering steps for rare or novel variants?
• How has your growing proficiency in variant annotation influenced your ability to contribute to multidisciplinary team (MDT) discussions regarding the clinical impact of genomic variations on patient care?

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.