These original educational practice questions demonstrate the explanation format and genetics reasoning used in our resources. They are not official certification examination items. References accompany the explanations where relevant.
Question 1 — Carrier Risk
Two parents are confirmed heterozygous carriers of the same fully penetrant autosomal recessive condition. Their child is known to be unaffected. Under the standard Mendelian model, what is that child's carrier probability?
Answer: C — 2/3
The four equally likely outcomes are AA, Aa, aA, and aa. Conditioning on unaffected status removes aa. Two of the three remaining outcomes are carriers, giving a probability of 2/3.
A (1/4) is the unconditional affected probability. B (1/2) is the carrier probability before unaffected status is considered. D (3/4) is the unconditional unaffected probability. The task is a conditional carrier calculation.
Question 2 — Bayesian Risk
A person has a 1/4 prior probability of carrying a familial variant. A hypothetical test has 90% sensitivity and 100% specificity. The result is negative. What is the residual carrier probability?
Answer: B — 1/31
The carrier-and-negative probability is 1/4 × 1/10 = 1/40. The noncarrier-and-negative probability is 3/4 = 30/40. Among negative results, the carrier probability is therefore 1/(1 + 30) = 1/31.
A ignores the prior. C ignores the test result. D assumes perfect sensitivity. These are deliberately hypothetical test characteristics and should not be applied to a real laboratory assay.
Question 3 — Counseling Response
During an optional genetic testing discussion, a client says, "If I have this variant, it will be my fault if my child inherits it." Which response best addresses the expressed concern first?
Answer: C
The client has expressed guilt. Exploring that concern allows the counselor to respond to its meaning and then provide accurate information. A may become useful but bypasses the concern. B offers false reassurance. D shifts to testing logistics before the client's concern has been addressed.
This teaching example applies the NSGC principles of respect for autonomy and client welfare. Source: NSGC Code of Ethics.
Question 4 — Variant Interpretation
A report identifies a variant of uncertain significance (VUS) in a gene plausibly related to a patient's findings. Which statement is most accurate?
Answer: D
Uncertain classification does not establish causality or benignity. A turns uncertainty into a diagnosis. B treats "not pathogenic" as benign. C can sometimes be part of a broader evaluation, but testing unaffected relatives does not by itself clarify the variant's significance. Appropriate clinical care can still follow the phenotype, and additional evidence may help clarify the variant over time.