Comprehensive Advanced Practice Genetics Nursing Certification
Examination on Hereditary Cancer and Cardiac Risk Assessment,
Pharmacogenomics, Prenatal and Pediatric Genetic Testing,
Ethical Counseling, Variant Interpretation, and Genomic
Healthcare Integration.
Questions 1–150
Question 1
A 45-year-old woman with bilateral breast cancer, triple-negative histology, and a family history of ovarian cancer in
her sister tests negative for a pathogenic *BRCA1/2* variant on standard sequencing. What is the most appropriate
next step?
A) Reassure the patient that hereditary cancer is ruled out
B) Order *BRCA1/2* duplication/deletion analysis
C) Recommend multigene panel testing including PALB2, CHEK2, and ATM
D) Proceed with risk-reducing mastectomy without further testing
Correct Answer: C
*Rationale: Triple-negative breast cancer and family history of ovarian cancer strongly suggest hereditary
predisposition despite negative BRCA1/2 sequencing. Multigene panels capture other moderate/high-risk genes not
detected by single-gene tests.*
Question 2
A patient undergoing exome sequencing for intellectual disability is found to have a variant of uncertain significance
(VUS) in a gene associated with autosomal dominant epilepsy. The parents are unaffected. What is the most
appropriate counseling approach?
A) Recommend prophylactic antiepileptic therapy
B) Interpret the VUS as likely benign due to lack of parental phenotype
C) Explain that a VUS cannot be used to guide clinical management at this time
D) Report the result as positive for epilepsy risk
Correct Answer: C
Rationale: VUS should not alter clinical management unless reclassified. Family segregation studies
may help, but the VUS alone is insufficient for diagnosis or treatment.
Question 3
In pharmacogenomic testing for clopidogrel, a patient is found to have two loss-of-function CYP2C19 alleles (*2/*2).
What is the expected clinical effect?
A) Increased bleeding risk
B) Reduced conversion of clopidogrel to its active metabolite, leading to higher risk of stent thrombosis
C) Enhanced antiplatelet effect
D) No change in drug metabolism
,Correct Answer: B
*Rationale: CYP2C19 loss-of-function alleles result in poor metabolizer status, reducing clopidogrel activation and
increasing risk for adverse cardiovascular events like stent thrombosis.*
Question 4
A couple both test positive for CFTR p.Phe508del heterozygosity. They are planning pregnancy. What is the recurrence
risk for cystic fibrosis in their child?
A) 0%
B) 25%
C) 50%
D) 75%
Correct Answer: B
Rationale: Cystic fibrosis follows autosomal recessive inheritance. Two carrier parents have a 25%
chance of an affected child (homozygous pathogenic variant) each pregnancy.
Question 5
A 30-year-old man presents with multiple colonic polyps (>100), congenital hypertrophy of the retinal pigment
epithelium (CHRPE), and a family history of desmoid tumors. Which genetic test is most appropriate?
A) MLH1 methylation analysis
B) APC gene sequencing and deletion/duplication analysis
C) MYH (MUTYH) biallelic testing
D) STK11 gene sequencing
Correct Answer: B
Rationale: CHRPE and desmoids are hallmark extracolonic manifestations of familial adenomatous
polyposis (FAP) due to pathogenic APC variants. MYH-associated polyposis lacks CHRPE.
Question 6
A patient undergoes noninvasive prenatal screening (NIPS) for common aneuploidies. The result shows high risk for
trisomy 18. What is the next best step?
A) Recommend termination of pregnancy based on NIPS
B) Offer diagnostic testing via amniocentesis or CVS
C) Repeat NIPS in 2 weeks
D) Order maternal serum alpha-fetoprotein (MSAFP)
Correct Answer: B
Rationale: NIPS is a screening test, not diagnostic. False positives occur. Confirmatory diagnostic
testing (karyotype or microarray on fetal cells) is required before irreversible decisions.
Question 7
Which of the following inheritance patterns is characterized by male-to-male transmission, absence of male-to-female
transmission, and all daughters of an affected male being carriers?
A) Autosomal dominant
B) Autosomal recessive
C) X-linked dominant
D) X-linked recessive
,Correct Answer: D
Rationale: X-linked recessive traits: affected males pass the variant to all daughters (carriers) but no
sons. Male-to-male transmission is absent.
Question 8
A patient with Li-Fraumeni syndrome (germline TP53 variant) is undergoing surveillance. Which imaging modality is
specifically recommended to reduce radiation exposure given the high risk of secondary malignancies?
A) Annual CT chest
B) Whole-body MRI annually
C) PET/CT every 6 months
D) Mammography starting at age 20
Correct Answer: B
*Rationale: Whole-body MRI avoids ionizing radiation, which is critical in TP53 carriers who are hypersensitive to
radiation-induced cancers.*
Question 9
A 25-year-old woman of Ashkenazi Jewish ancestry is found to have a BRCA1 c.68_69delAG (185delAG) variant. She
has no personal cancer history. What is the estimated lifetime risk of breast cancer by age 70?
A) 20–30%
B) 40–50%
C) 55–65%
D) 70–80%
Correct Answer: C
Rationale: BRCA1 pathogenic variants confer ~55–65% lifetime breast cancer risk (some studies up to
72%). Ashkenazi founder variant 185delAG is high penetrance.
Question 10
During pre-test genetic counseling for Huntington disease, the patient asks, “If I test positive, when will symptoms
start?” What is the most accurate response?
A) Symptoms will begin exactly at the median age of onset for your family
B) The CAG repeat length correlates with age of onset, but prediction is imprecise
C) Positive results guarantee onset before age 50
D) Only symptomatic individuals can be tested for Huntington disease
Correct Answer: B
Rationale: Inverse correlation between CAG repeat length and age of onset exists, but marked
variability and modifying factors prevent precise prediction.
Question 11
A 58-year-old man with metastatic prostate cancer, intraductal histology, and a brother with pancreatic cancer tests
positive for BRCA2 c.5946delT (6174delT). What is the most appropriate therapy consideration?
A) Androgen deprivation therapy alone
B) PARP inhibitor (e.g., olaparib)
C) Checkpoint inhibitor (pembrolizumab)
D) Carboplatin monotherapy
, Correct Answer: B
*Rationale: PARP inhibitors exploit synthetic lethality in BRCA2-deficient tumors. FDA approved for BRCA-mutated
metastatic castration-resistant prostate cancer.*
Question 12
A couple has a child with spinal muscular atrophy (SMA) type 1 due to homozygous deletion of SMN1 exon 7. The
parents are both carriers. For their next pregnancy, which prenatal test directly detects the fetal SMN1 copy number?
A) Maternal serum PAPP-A
B) Quad screen
C) MLPA or quantitative PCR on CVS or amniotic fluid
D) Noninvasive prenatal screening for SMA
Correct Answer: C
Rationale: MLPA or qPCR quantifies SMN1 exon 7 copies on fetal DNA from invasive sampling. NIPS
for SMA is emerging but not standard diagnostic.
Question 13
What is the primary limitation of direct-to-consumer (DTC) genetic testing for disease risk from a genetics nursing
perspective?
A) Tests are always inaccurate
B) Lack of pre- and post-test counseling and false reassurance or unnecessary anxiety
C) DTC tests cannot detect any pathogenic variants
D) They are illegal in most states
Correct Answer: B
Rationale: Major concerns include misinterpretation of low-risk variants, absence of professional
counseling, and lack of clinical validation for many SNPs.
Question 14
A patient with hereditary hemochromatosis (homozygous C282Y in HFE) has ferritin of 1200 ng/mL and transferrin
saturation 85%. What is the first-line management?
A) High-dose vitamin C
B) Phlebotomy induction therapy
C) Oral iron chelation
D) Liver biopsy before intervention
Correct Answer: B
*Rationale: Phlebotomy removes excess iron. Initiate when ferritin >300 (men) or >200 (women) with elevated
saturation. Chelation not first-line in hemochromatosis.*
Question 15
A 32-year-old woman has a 5-year-old son with fragile X syndrome (full mutation >200 CGG repeats, abnormal
methylation). She is considering another pregnancy. Her FMR1 CGG repeat count is 88. What is her risk of having
another affected son?
A) <1%
B) 50%
C) 100%
D) 0%
Examination on Hereditary Cancer and Cardiac Risk Assessment,
Pharmacogenomics, Prenatal and Pediatric Genetic Testing,
Ethical Counseling, Variant Interpretation, and Genomic
Healthcare Integration.
Questions 1–150
Question 1
A 45-year-old woman with bilateral breast cancer, triple-negative histology, and a family history of ovarian cancer in
her sister tests negative for a pathogenic *BRCA1/2* variant on standard sequencing. What is the most appropriate
next step?
A) Reassure the patient that hereditary cancer is ruled out
B) Order *BRCA1/2* duplication/deletion analysis
C) Recommend multigene panel testing including PALB2, CHEK2, and ATM
D) Proceed with risk-reducing mastectomy without further testing
Correct Answer: C
*Rationale: Triple-negative breast cancer and family history of ovarian cancer strongly suggest hereditary
predisposition despite negative BRCA1/2 sequencing. Multigene panels capture other moderate/high-risk genes not
detected by single-gene tests.*
Question 2
A patient undergoing exome sequencing for intellectual disability is found to have a variant of uncertain significance
(VUS) in a gene associated with autosomal dominant epilepsy. The parents are unaffected. What is the most
appropriate counseling approach?
A) Recommend prophylactic antiepileptic therapy
B) Interpret the VUS as likely benign due to lack of parental phenotype
C) Explain that a VUS cannot be used to guide clinical management at this time
D) Report the result as positive for epilepsy risk
Correct Answer: C
Rationale: VUS should not alter clinical management unless reclassified. Family segregation studies
may help, but the VUS alone is insufficient for diagnosis or treatment.
Question 3
In pharmacogenomic testing for clopidogrel, a patient is found to have two loss-of-function CYP2C19 alleles (*2/*2).
What is the expected clinical effect?
A) Increased bleeding risk
B) Reduced conversion of clopidogrel to its active metabolite, leading to higher risk of stent thrombosis
C) Enhanced antiplatelet effect
D) No change in drug metabolism
,Correct Answer: B
*Rationale: CYP2C19 loss-of-function alleles result in poor metabolizer status, reducing clopidogrel activation and
increasing risk for adverse cardiovascular events like stent thrombosis.*
Question 4
A couple both test positive for CFTR p.Phe508del heterozygosity. They are planning pregnancy. What is the recurrence
risk for cystic fibrosis in their child?
A) 0%
B) 25%
C) 50%
D) 75%
Correct Answer: B
Rationale: Cystic fibrosis follows autosomal recessive inheritance. Two carrier parents have a 25%
chance of an affected child (homozygous pathogenic variant) each pregnancy.
Question 5
A 30-year-old man presents with multiple colonic polyps (>100), congenital hypertrophy of the retinal pigment
epithelium (CHRPE), and a family history of desmoid tumors. Which genetic test is most appropriate?
A) MLH1 methylation analysis
B) APC gene sequencing and deletion/duplication analysis
C) MYH (MUTYH) biallelic testing
D) STK11 gene sequencing
Correct Answer: B
Rationale: CHRPE and desmoids are hallmark extracolonic manifestations of familial adenomatous
polyposis (FAP) due to pathogenic APC variants. MYH-associated polyposis lacks CHRPE.
Question 6
A patient undergoes noninvasive prenatal screening (NIPS) for common aneuploidies. The result shows high risk for
trisomy 18. What is the next best step?
A) Recommend termination of pregnancy based on NIPS
B) Offer diagnostic testing via amniocentesis or CVS
C) Repeat NIPS in 2 weeks
D) Order maternal serum alpha-fetoprotein (MSAFP)
Correct Answer: B
Rationale: NIPS is a screening test, not diagnostic. False positives occur. Confirmatory diagnostic
testing (karyotype or microarray on fetal cells) is required before irreversible decisions.
Question 7
Which of the following inheritance patterns is characterized by male-to-male transmission, absence of male-to-female
transmission, and all daughters of an affected male being carriers?
A) Autosomal dominant
B) Autosomal recessive
C) X-linked dominant
D) X-linked recessive
,Correct Answer: D
Rationale: X-linked recessive traits: affected males pass the variant to all daughters (carriers) but no
sons. Male-to-male transmission is absent.
Question 8
A patient with Li-Fraumeni syndrome (germline TP53 variant) is undergoing surveillance. Which imaging modality is
specifically recommended to reduce radiation exposure given the high risk of secondary malignancies?
A) Annual CT chest
B) Whole-body MRI annually
C) PET/CT every 6 months
D) Mammography starting at age 20
Correct Answer: B
*Rationale: Whole-body MRI avoids ionizing radiation, which is critical in TP53 carriers who are hypersensitive to
radiation-induced cancers.*
Question 9
A 25-year-old woman of Ashkenazi Jewish ancestry is found to have a BRCA1 c.68_69delAG (185delAG) variant. She
has no personal cancer history. What is the estimated lifetime risk of breast cancer by age 70?
A) 20–30%
B) 40–50%
C) 55–65%
D) 70–80%
Correct Answer: C
Rationale: BRCA1 pathogenic variants confer ~55–65% lifetime breast cancer risk (some studies up to
72%). Ashkenazi founder variant 185delAG is high penetrance.
Question 10
During pre-test genetic counseling for Huntington disease, the patient asks, “If I test positive, when will symptoms
start?” What is the most accurate response?
A) Symptoms will begin exactly at the median age of onset for your family
B) The CAG repeat length correlates with age of onset, but prediction is imprecise
C) Positive results guarantee onset before age 50
D) Only symptomatic individuals can be tested for Huntington disease
Correct Answer: B
Rationale: Inverse correlation between CAG repeat length and age of onset exists, but marked
variability and modifying factors prevent precise prediction.
Question 11
A 58-year-old man with metastatic prostate cancer, intraductal histology, and a brother with pancreatic cancer tests
positive for BRCA2 c.5946delT (6174delT). What is the most appropriate therapy consideration?
A) Androgen deprivation therapy alone
B) PARP inhibitor (e.g., olaparib)
C) Checkpoint inhibitor (pembrolizumab)
D) Carboplatin monotherapy
, Correct Answer: B
*Rationale: PARP inhibitors exploit synthetic lethality in BRCA2-deficient tumors. FDA approved for BRCA-mutated
metastatic castration-resistant prostate cancer.*
Question 12
A couple has a child with spinal muscular atrophy (SMA) type 1 due to homozygous deletion of SMN1 exon 7. The
parents are both carriers. For their next pregnancy, which prenatal test directly detects the fetal SMN1 copy number?
A) Maternal serum PAPP-A
B) Quad screen
C) MLPA or quantitative PCR on CVS or amniotic fluid
D) Noninvasive prenatal screening for SMA
Correct Answer: C
Rationale: MLPA or qPCR quantifies SMN1 exon 7 copies on fetal DNA from invasive sampling. NIPS
for SMA is emerging but not standard diagnostic.
Question 13
What is the primary limitation of direct-to-consumer (DTC) genetic testing for disease risk from a genetics nursing
perspective?
A) Tests are always inaccurate
B) Lack of pre- and post-test counseling and false reassurance or unnecessary anxiety
C) DTC tests cannot detect any pathogenic variants
D) They are illegal in most states
Correct Answer: B
Rationale: Major concerns include misinterpretation of low-risk variants, absence of professional
counseling, and lack of clinical validation for many SNPs.
Question 14
A patient with hereditary hemochromatosis (homozygous C282Y in HFE) has ferritin of 1200 ng/mL and transferrin
saturation 85%. What is the first-line management?
A) High-dose vitamin C
B) Phlebotomy induction therapy
C) Oral iron chelation
D) Liver biopsy before intervention
Correct Answer: B
*Rationale: Phlebotomy removes excess iron. Initiate when ferritin >300 (men) or >200 (women) with elevated
saturation. Chelation not first-line in hemochromatosis.*
Question 15
A 32-year-old woman has a 5-year-old son with fragile X syndrome (full mutation >200 CGG repeats, abnormal
methylation). She is considering another pregnancy. Her FMR1 CGG repeat count is 88. What is her risk of having
another affected son?
A) <1%
B) 50%
C) 100%
D) 0%
