Prenatal Genomics —
Training activity: 6

Details

Analyse, interpret and report the results of cases referred due to a family history of a genomic condition, to include:

• Segregation analysis
• Targeted molecular tests

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 learning outcomes to ensure you are prepared to apply appropriate testing strategies for family history, interpret chromosomal rearrangements and recurrence risk, and use bioinformatic tools to investigate genomic variants?
• What essential knowledge have you identified as necessary regarding the principles of Mendelian inheritance and the ethical and legal dimensions of prenatal diagnosis before you begin the activity?
• Have you considered how your reporting must include appropriate recommendations for patient management, specifically addressing the implications for the family and recurrence risks?

What do you anticipate you will learn from the experience?

• What specific insights do you hope to gain regarding the importance of segregation analysis in confirming inheritance patterns and the integration of molecular findings with detailed family history?
• What is your existing knowledge of targeted molecular tests and the technical limitations of prenatal testing, such as maternal cell contamination (MCC), mosaicism, or allele drop-out?
• In what ways do you anticipate developing your skills in navigating the ethical complexities of reporting findings that may have significant implications for extended family members?
• How do you anticipate this activity will improve your ability to use best practice guidelines and bioinformatic tools to determine the clinical significance of familial variants?

What actions will you take in preparation for the experience?

• How have you prepared for your discussion with your Training Officer to gain clarity on the expected standards for analysing complex pedigrees and performing segregation analysis?
• Which specific resources, such as standard reporting templates for familial cases, variant databases, or national guidelines for prenatal testing, have you reviewed to ensure your approach is evidence-based?
• Have you identified the potential challenges of dealing with incomplete family histories or interpreting unexpected results, such as a variant that does not segregate as anticipated?
• How do you feel about embarking on this activity, particularly given the sensitive nature of familial testing and its impact on multiple family members?
• What actions have you taken to familiarise yourself with the legal aspects of the unborn foetus to ensure your interpretation and recommendations remain within the scope of practice?

In action

What are you doing?

• How are you currently approaching the segregation analysis for this familial case, and why have you chosen this particular sequence of steps—such as reviewing the pedigree before assessing the targeted molecular data?
• What decisions are you making right now as you evaluate whether the fetal result matches the expected Mendelian inheritance pattern for the known familial variant?
• What specific features of the genomic data are you focusing on to confirm or exclude the familial condition, and how are you characterising any chromosomal rearrangements identified?
• What aspects of your practice feel intuitive, such as identifying standard inheritance patterns, and what requires more conscious effort, such as using bioinformatic tools to investigate the clinical significance of unexpected variants?

How are you progressing with the activity?

• How effective are your current strategies in identifying and characterising the relevant genomic abnormalities that explain the family history?
• What challenges are you encountering in this moment, such as encountering an unexpected foetal result relative to parental samples, or technical issues like maternal cell contamination (MCC) and allele drop-out?
• How does this specific case connect to your existing knowledge of the maternity clinical care pathway and the legal and ethical dimensions of prenatal diagnosis?
• What are you learning about the practical application of segregation theory as the data unfolds, especially if you encounter a variant of uncertain significance (VUS) alongside the known mutation?

How are you adapting to the situation?

• Are there alternative analysis or interpretation approaches you are considering, such as employing alternative filtering strategies or checking for mosaicism, if the initial results are unclear or discordant with the family history?
• What immediate support or guidance do you feel you need from a senior clinical scientist regarding the ethical implications of reporting incidental findings or complex recurrence risks?
• How are you ensuring that your interpretation and draft report remain within your scope of practice, particularly when formulating management recommendations for the pregnancy?
• In what ways are you adjusting your reporting style to ensure that the implications for the extended family and future testing are communicated clearly and sensitively?

On action

What did you notice?

• How would you summarise the key points of your experience in analysing and reporting results for cases with a family history of a genomic condition, specifically regarding the targeted molecular tests and segregation analysis performed?
• What specific events or interactions felt most important during the process, such as the interpretation of a complex family pedigree or identifying how a familial variant segregated (or failed to segregate) in the foetal sample?
• Which ‘reflect-in-action’ moments did you notice where you had to adapt your approach—for example, by immediately consulting external variant databases upon identifying an unrelated variant of uncertain significance (VUS) or an unexpected inheritance pattern?
• How did you feel while managing cases with significant implications for multiple family members, particularly when the results directly influenced recurrence risk or subsequent pregnancy management?

What did you learn from the activity?

• What specific skills or knowledge did you develop regarding the application of testing strategies for familial disorders and the use of bioinformatic tools to investigate the clinical significance of variants?
• How did you improve your ability to interpret chromosomal rearrangements and genomic variants (including copy number changes) while adhering to best practice guidelines?
• In what ways did your real-time decisions—such as seeking advice on the ethical and legal dimensions of reporting incidental findings—influence the final report and the recommendations for patient management?
• How does this experience relate to the requirements for post-programme practice as a Clinical Scientist, particularly in ensuring that segregation analysis is meticulous and clearly communicated to clinicians and families?

What will you take from the experience moving forward?

• What areas for continued development have been identified, such as a need for further training on complex inheritance patterns or the legal aspects of the unborn foetus?
• How can you apply the learning from this activity to your routine practice—for example, by systematically checking the pedigree structure against the predicted inheritance pattern before proceeding to molecular data analysis?
• What specific ‘next steps’ will you take to consolidate your learning, such as reviewing standard reporting templates for familial cases or resources on specific genomic conditions?
• What support or resources have you identified as necessary for further development, such as access to expert mentorship for sensitive reporting or specialised variant interpretation committees?

Beyond action

Have you revisited the experiences?

• How have you re-evaluated your initial interpretations of familial variant segregation and pedigree structures now that you have encountered more complex cases in clinical practice?
• Have you reviewed your actions from previous reflections for this activity to determine if you have completed identified tasks, such as reviewing the ethical and legal dimensions of prenatal diagnosis or the legislation associated with the unborn foetus?
• How has your view of these situations changed through professional storytelling with peers or senior colleagues regarding the challenges of reporting incidental findings or Variants of Uncertain Significance (VUS) discovered during targeted familial testing?
• How do your experiences with prenatal familial cases compare with your analysis of familial cases in other modules, such as cancer predisposition or adult-onset disorders, and what observable practices (e.g., systematic pedigree review) have you assimilated across these areas?
• Have your decisions regarding recurrence risk and recommendations for future testing evolved since completing this activity, particularly after discussing case outcomes in multidisciplinary team (MDT) meetings?

How have these experiences impacted upon your current practice?

• In what ways has the accumulated learning from performing segregation analysis supported your preparation for ‘in-person’ assessments, specifically Case-Based Discussions regarding testing strategies for patients with a family history?
• How has your understanding of the maternity clinical care pathway influenced your current approach to integrating molecular findings with clinical and family history to provide a clear diagnosis?
• How effectively are you now able to use bioinformatic tools and best practice guidelines to investigate the clinical significance of variants compared to your initial attempts during this training activity?
• How has this experience contributed to your ability to deliver a safe and high-quality service by accurately communicating the implications of results for extended family members?
• Can you identify specific instances where your foundational knowledge of Mendelian inheritance and targeted molecular tests has informed your problem-solving in subsequent, unrelated prenatal cases?

How might these experiences contribute towards your future practice?

• What transferable skills in diagnostic planning and clinical reasoning have you developed that will help you evaluate and adopt new technologies, such as whole exome sequencing for family trios?
• What clear actions for continued development have you identified to ensure you stay current with evolving national guidelines for prenatal diagnosis and familial testing?
• How will your understanding of technical limitations—such as maternal cell contamination (MCC), mosaicism, and allele drop-out—inform your approach to troubleshooting new assays in the future?
• How will your appreciation for the ethical complexities discussed in this forum help you navigate future service improvements or innovations in the prenatal genomic pathway?
• How has this activity shaped your long-term goals for mastering the interpretation of complex chromosomal rearrangements?

Relevant learning outcomes

#	Outcome
# 3	Outcome Apply appropriate testing strategies to patients with a family history of a genetic disorder.
# 4	Outcome Interpret chromosomal rearrangements, including implications for recurrence risk and future testing.
# 5	Outcome Interpret genomic variants, including copy number changes and investigate the clinical significance of variants using bioinformatic tools using best practice guidelines.
# 6	Outcome Interpret and report prenatal genomic findings, including appropriate recommendations for patient management.