Paediatric Genomics —
Training activity: 9

Details

Interpret and report Copy Number Variants for patients with clinical features highly suggestive of a chromosomal cause

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?

• Have you reviewed the specific learning outcomes to ensure you are prepared to apply appropriate testing strategies for patients referred with increased screening risk, abnormal ultrasound findings, or a family history of genetic disorders?
• What essential knowledge have you identified as necessary regarding the principles of aCGH and karyotyping, the various types of CNVs, and the specific nomenclature used to describe these abnormalities before you begin?
• How do you intend to demonstrate that your interpretations and reports follow best practice guidelines and provide appropriate recommendations for patient management?

What do you anticipate you will learn from the experience?

• What specific insights have you considered gaining regarding the assessment of the clinical significance of CNVs and the correlation between cytogenetic and molecular findings?
• How have you reflected on your existing knowledge of genomic variants to determine how this activity will improve your proficiency with bioinformatic tools?
• What new skills have you anticipated developing in order to write clear, informative reports that integrate complex prenatal genomic findings?

What actions will you take in preparation for the experience?

• What specific points have you prepared to discuss with your Training Officer, or with bioinformaticians and clinical geneticists, to ensure you have a clear understanding of the task’s complexities?
• Which examples of array and karyotype reports have you selected to review as part of your preparation for interpreting and reporting these abnormalities?
• How have you planned to handle the possible challenges of interpreting Variants of Uncertain Significance (VUS), novel CNVs, or incidental findings?
• How have you identified your feelings about embarking on this activity, particularly regarding the sensitivity of reporting findings that impact prenatal management decisions?
• Which professional guidelines and standard operating procedures have you identified to ensure your interpretation of genomic dosage and chromosomal structure remains within your scope of practice?

In action

What are you doing?

• How are you currently approaching the interpretation of copy number variant (CNV) data obtained from array-based technologies (aCGH/SNP) or conventional karyotyping, and why have you chosen this specific sequence of steps?
• What specific features are you focusing on right now—such as gains, losses, size, or gene content—and how are you determining their importance in the context of the clinical referral?
• What decisions are you making in this moment regarding the clinical significance of identified variants, particularly when considering their presence in pathogenic or benign databases?
• What aspects of your practice in applying testing strategies for increased screening risk or abnormal scans feel intuitive, and which require a more conscious effort to align with best practice guidelines?

How are you progressing with the activity?

• How effectively are your chosen methods allowing you to identify and characterise genomic abnormalities that might explain clinical features suggestive of a chromosomal cause?
• What challenges are you encountering right now, such as resolving discrepancies between different technologies (e.g., QFPCR vs. Microarray) or interpreting variants of uncertain significance (VUS)?
• In what ways is this activity connecting to your existing knowledge of Mendelian inheritance patterns, gene dosage effects, and chromosomal rearrangements?
• How are you integrating the potential implications for recurrence risk and future testing into your interpretation as the results unfold?

How are you adapting to the situation?

• What alternative analysis or interpretation strategies are you considering if your initial assessment of a variant is unclear or if the clinical significance remains ambiguous?
• How are you deciding when to seek immediate advice or clarification from a senior colleague, clinical geneticist, or bioinformatician regarding a complex or novel rearrangement?
• How are you ensuring that your interpretation and recommendations for patient management remain strictly within your scope of practice and adhere to relevant professional nomenclature (ISCN)?
• How are you adjusting your reporting style to ensure it clearly addresses the clinical question raised by an abnormal prenatal scan or a family history of a genetic disorder?

On action

What did you notice?

• How would you summarise the key findings of the cases you reviewed, including the range of copy number variants (CNVs) such as microdeletions, microduplications, or larger structural rearrangements?
• What specific details did you notice regarding the referral reasons, such as abnormal ultrasound findings or a family history of a genetic disorder, and how did these influence your initial approach?
• In what ways did you notice the different levels of detail or discordance between results from array-based comparative genomic hybridisation (aCGH) and conventional karyotyping?
• What ‘reflect-in-action’ moments did you notice where you had to adjust your interpretation based on emerging data or technical limitations?

What did you learn from the activity?

• What specific skills or knowledge did you develop regarding the assessment of variant pathogenicity using bioinformatic tools and best practice guidelines?
• How did you improve your ability to interpret complex chromosomal rearrangements and evaluate their implications for a patient’s recurrence risk and future testing?
• What did you learn from any unexpected challenges, such as interpreting variants of uncertain significance (VUS) or incidental findings that did not immediately align with the clinical features?
• How did your real-time decisions during the interpretation process influence the final recommendations you made for patient management in the interpretive report?
• In what ways does this experience relate to the requirements for your future post-programme practice as a Clinical Scientist responsible for independent reporting in a clinical setting?

What will you take from the experience moving forward?

• What areas for continued development have you identified, such as a need to enhance your proficiency with specific CNV databases like DECIPHER or ISCA?
• How will you apply the systematic approach to reviewing inheritance patterns and literature that you practiced during this activity to your routine clinical work?
• What specific steps will you now plan to take to consolidate your learning, such as attending workshops on cytogenomics or reviewing genotype-phenotype correlations for specific abnormalities?
• What support or resources have you identified as necessary for your ongoing development, such as access to expert mentorship from clinical geneticists or bioinformaticians for complex cases?
• How will you ensure that your future reporting consistently adheres to relevant professional guidelines and international nomenclature (ISCN)?

Beyond action

Have you revisited the experiences?

• How have you re-evaluated your initial interpretations of copy number variants (CNVs) and chromosomal rearrangements in light of new learning regarding their clinical significance and pathogenicity?
• In what ways have you assimilated behaviours and practices you previously observed in the Observed Training Activities (OTAs), such as classifying variants or identifying appropriate referrals?
• As you review your reflections across both the Paediatric and Prenatal Genomics modules, what overarching themes or patterns have you identified regarding your ability to integrate results from multiple technologies like QFPCR, microarrays, and karyotyping?
• How has engaging in professional storytelling or case discussions with clinical geneticists and senior colleagues shifted your perspective on the complex genotype-phenotype correlations you encountered?

How have these experiences impacted upon your current practice?

• How have you applied your increased proficiency in using online databases and best practice guidelines for variant interpretation to your routine clinical workload?
• In what ways has your experience with CNV interpretation influenced how you now approach more complex genomic datasets, such as searching for structural variants in whole genome sequencing (WGS) data?
• How have you integrated your understanding of recurrence risk and management recommendations into your current reporting practices for patients with family histories of genetic disorders?
• How has your knowledge of the correlation between abnormal ultrasound findings and genomic abnormalities improved the way you communicate results or provide advice to other healthcare professionals?
• How have you applied the skills gained from this activity to subsequent prenatal cases, particularly when navigating the sensitivities of increased screening risks?

How might these experiences contribute towards your future practice?

• What transferable skills in diagnostic planning and articulating the strengths and limitations of different cytogenetic techniques have you identified as essential for your future role as a Clinical Scientist?
• What clear actions have you defined for your continued professional development, such as staying updated on advancements in bioinformatic tools or evolving national guidelines for prenatal genomic findings?
• How will your experience in integrating diverse genomic data for full interpretation support your ability to lead or contribute to future service improvements and innovations?
• How has your appreciation for the ethical and legal dimensions of prenatal testing, often discussed in multidisciplinary team (MDT) meetings, shaped the approach you will take towards patient-centred care in your future career?

Relevant learning outcomes

#	Outcome
# 1	Outcome Apply appropriate testing strategies to patients referred for paediatric disorders.
# 3	Outcome Perform whole genome analysis for patients referred for paediatric disorders.
# 4	Outcome Interpret genomic variants, including copy number changes, and investigate the clinical significance of variants using bioinformatic tools using best practice guidelines.
# 5	Outcome Interpret and report genomic testing relevant to paediatric conditions, including appropriate recommendations for patient management.