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 42-year-old woman with bilateral breast cancer (ER/PR negative, HER2 negative) and a sister with ovarian cancer at
age 44 undergoes germline genetic testing. A BRCA1 variant of uncertain significance (VUS) is identified. What is the
most appropriate clinical management?
A) Recommend bilateral mastectomy based on family history
B) Manage based on the VUS as if it were pathogenic
C) Manage based on personal and family history, not the VUS
D) Recommend risk-reducing salpingo-oophorectomy immediately
Correct Answer: C
Rationale: A VUS should not be used to guide clinical management. Risk assessment should rely on
personal and family history until the VUS is reclassified.
Question 2
A 60-year-old man with metastatic castration-resistant prostate cancer (mCRPC) has a brother with breast cancer at
age 55. Tumor sequencing reveals a BRCA2 pathogenic variant. What is the most appropriate targeted therapy?
A) Enzalutamide
B) Olaparib
C) Abiraterone
D) Docetaxel
Correct Answer: B
Rationale: PARP inhibitors (olaparib, rucaparib) are FDA approved for BRCA-mutated mCRPC after
prior treatment with novel hormonal agents.
Question 3
A couple both test positive for CFTR p.Phe508del heterozygosity and are planning pregnancy. What is the risk that
their child will have cystic fibrosis?
A) 0%
B) 25%
C) 50%
D) 75%
Correct Answer: B
Rationale: Cystic fibrosis is autosomal recessive. Two carriers have a 25% chance of an affected child
(homozygous) per pregnancy.
,Question 4
A 25-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 gene is most likely responsible?
A) MLH1
B) APC
C) MUTYH
D) STK11
Correct Answer: B
Rationale: CHRPE and desmoids are hallmark extracolonic manifestations of familial adenomatous
polyposis (FAP) due to APC pathogenic variants.
Question 5
A patient undergoing noninvasive prenatal screening (NIPS) receives a high-risk result for trisomy 21. What is the next
best step?
A) Terminate the pregnancy based on NIPS
B) Offer diagnostic testing via amniocentesis or CVS
C) Repeat NIPS in 2 weeks
D) Order maternal serum alpha-fetoprotein
Correct Answer: B
Rationale: NIPS is a screening test, not diagnostic. Confirmatory diagnostic testing (karyotype or
microarray on fetal cells) is required.
Question 6
A 32-year-old woman with a BRCA1 pathogenic variant has no personal cancer history. What is her estimated lifetime
risk of ovarian cancer by age 70?
A) 10-20%
B) 30-40%
C) 40-60%
D) 70-80%
Correct Answer: C
*Rationale: BRCA1 pathogenic variants confer a 40-60% lifetime risk of ovarian cancer. BRCA2 confers 15-20% risk.*
Question 7
A patient with Li-Fraumeni syndrome (germline TP53 variant) requires surveillance imaging. Which modality is
specifically preferred to minimize radiation exposure?
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 secondary malignancies.*
,Question 8
A 55-year-old man with hereditary hemochromatosis (homozygous C282Y) has ferritin 1500 ng/mL and transferrin
saturation 85%. He has no diabetes, arthritis, or liver enzyme elevation. What is the most appropriate next step?
A) Observation with annual ferritin
B) Phlebotomy weekly until ferritin <50 ng/mL
C) Liver biopsy
D) Oral deferasirox
Correct Answer: B
*Rationale: Phlebotomy is indicated for ferritin >300 ng/mL in men regardless of symptoms to prevent organ damage
(cirrhosis, diabetes, cardiomyopathy).*
Question 9
A 30-year-old woman with a BRCA2 pathogenic variant and a family history of pancreatic cancer (father at age 52)
asks about pancreatic cancer screening. At what age should screening begin?
A) Age 40
B) Age 42 (10 years before youngest family case)
C) Age 50
D) No screening recommended
Correct Answer: B
*Rationale: Screening (EUS or MRI) should begin at age 50 or 10 years before the earliest pancreatic cancer in the
family, whichever is earlier. 52 − 10 = 42 years.*
Question 10
A 40-year-old woman with a BRCA1 pathogenic variant undergoes risk-reducing bilateral salpingo-oophorectomy
(BSO) at age 38. Pathology is benign. She requests hormone replacement therapy (HRT) for severe vasomotor
symptoms. What is the recommendation?
A) HRT is contraindicated in BRCA1 carriers
B) Short-term HRT until natural menopause age (51) is safe and does not increase breast cancer risk
C) Only vaginal estrogen is allowed
D) HRT increases ovarian cancer risk
Correct Answer: B
*Rationale: Short-term HRT after BSO in BRCA1 carriers is safe and does not negate the breast cancer risk reduction
from BSO.*
Question 11
A 28-year-old man presents with tall stature, gynecomastia, small firm testes, and azoospermia. FSH is 25 IU/L
(elevated). What is the most likely karyotype?
A) 47,XXY
B) 47,XYY
C) 46,XX
D) 45,X/46,XY
Correct Answer: A
, Rationale: Klinefelter syndrome (47,XXY) presents with hypergonadotropic hypogonadism, small
testes, gynecomastia, and infertility.
Question 12
A patient with a CYP2C19 poor metabolizer phenotype (*2/*2) is prescribed clopidogrel after drug-eluting stent
placement. What is the expected clinical outcome?
A) Normal antiplatelet effect
B) Reduced active metabolite formation, increased risk of stent thrombosis
C) Increased bleeding risk
D) Enhanced platelet inhibition
Correct Answer: B
*Rationale: CYP2C19 poor metabolizers cannot convert clopidogrel to its active metabolite, leading to high on-
treatment platelet reactivity and increased thrombotic risk.*
Question 13
A 32-year-old woman with a BRCA1 pathogenic variant is 10 weeks pregnant. She requests prenatal diagnosis for the
familial variant. What is the earliest gestational age for chorionic villus sampling (CVS)?
A) 6 weeks
B) 10-13 weeks
C) 15 weeks
D) 18 weeks
Correct Answer: B
*Rationale: CVS is performed at 10-13 weeks gestation. Amniocentesis is performed at 15-20 weeks.*
Question 14
A 6-month-old infant presents with progressive macrocephaly, irritability, loss of developmental milestones, and
cherry-red spots on macula. Enzyme assay shows hexosaminidase A deficiency. What is the inheritance pattern?
A) Autosomal dominant
B) Autosomal recessive
C) X-linked dominant
D) Mitochondrial
Correct Answer: B
Rationale: Tay-Sachs disease (HEXA deficiency) is autosomal recessive, most common in Ashkenazi
Jewish population.
Question 15
A 45-year-old woman with Lynch syndrome (MSH2 pathogenic variant) undergoes annual colonoscopy. A 5 mm
sessile serrated polyp is removed. What is the recommended surveillance interval?
A) 1 year
B) 3 years
C) 5 years
D) 10 years
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 42-year-old woman with bilateral breast cancer (ER/PR negative, HER2 negative) and a sister with ovarian cancer at
age 44 undergoes germline genetic testing. A BRCA1 variant of uncertain significance (VUS) is identified. What is the
most appropriate clinical management?
A) Recommend bilateral mastectomy based on family history
B) Manage based on the VUS as if it were pathogenic
C) Manage based on personal and family history, not the VUS
D) Recommend risk-reducing salpingo-oophorectomy immediately
Correct Answer: C
Rationale: A VUS should not be used to guide clinical management. Risk assessment should rely on
personal and family history until the VUS is reclassified.
Question 2
A 60-year-old man with metastatic castration-resistant prostate cancer (mCRPC) has a brother with breast cancer at
age 55. Tumor sequencing reveals a BRCA2 pathogenic variant. What is the most appropriate targeted therapy?
A) Enzalutamide
B) Olaparib
C) Abiraterone
D) Docetaxel
Correct Answer: B
Rationale: PARP inhibitors (olaparib, rucaparib) are FDA approved for BRCA-mutated mCRPC after
prior treatment with novel hormonal agents.
Question 3
A couple both test positive for CFTR p.Phe508del heterozygosity and are planning pregnancy. What is the risk that
their child will have cystic fibrosis?
A) 0%
B) 25%
C) 50%
D) 75%
Correct Answer: B
Rationale: Cystic fibrosis is autosomal recessive. Two carriers have a 25% chance of an affected child
(homozygous) per pregnancy.
,Question 4
A 25-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 gene is most likely responsible?
A) MLH1
B) APC
C) MUTYH
D) STK11
Correct Answer: B
Rationale: CHRPE and desmoids are hallmark extracolonic manifestations of familial adenomatous
polyposis (FAP) due to APC pathogenic variants.
Question 5
A patient undergoing noninvasive prenatal screening (NIPS) receives a high-risk result for trisomy 21. What is the next
best step?
A) Terminate the pregnancy based on NIPS
B) Offer diagnostic testing via amniocentesis or CVS
C) Repeat NIPS in 2 weeks
D) Order maternal serum alpha-fetoprotein
Correct Answer: B
Rationale: NIPS is a screening test, not diagnostic. Confirmatory diagnostic testing (karyotype or
microarray on fetal cells) is required.
Question 6
A 32-year-old woman with a BRCA1 pathogenic variant has no personal cancer history. What is her estimated lifetime
risk of ovarian cancer by age 70?
A) 10-20%
B) 30-40%
C) 40-60%
D) 70-80%
Correct Answer: C
*Rationale: BRCA1 pathogenic variants confer a 40-60% lifetime risk of ovarian cancer. BRCA2 confers 15-20% risk.*
Question 7
A patient with Li-Fraumeni syndrome (germline TP53 variant) requires surveillance imaging. Which modality is
specifically preferred to minimize radiation exposure?
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 secondary malignancies.*
,Question 8
A 55-year-old man with hereditary hemochromatosis (homozygous C282Y) has ferritin 1500 ng/mL and transferrin
saturation 85%. He has no diabetes, arthritis, or liver enzyme elevation. What is the most appropriate next step?
A) Observation with annual ferritin
B) Phlebotomy weekly until ferritin <50 ng/mL
C) Liver biopsy
D) Oral deferasirox
Correct Answer: B
*Rationale: Phlebotomy is indicated for ferritin >300 ng/mL in men regardless of symptoms to prevent organ damage
(cirrhosis, diabetes, cardiomyopathy).*
Question 9
A 30-year-old woman with a BRCA2 pathogenic variant and a family history of pancreatic cancer (father at age 52)
asks about pancreatic cancer screening. At what age should screening begin?
A) Age 40
B) Age 42 (10 years before youngest family case)
C) Age 50
D) No screening recommended
Correct Answer: B
*Rationale: Screening (EUS or MRI) should begin at age 50 or 10 years before the earliest pancreatic cancer in the
family, whichever is earlier. 52 − 10 = 42 years.*
Question 10
A 40-year-old woman with a BRCA1 pathogenic variant undergoes risk-reducing bilateral salpingo-oophorectomy
(BSO) at age 38. Pathology is benign. She requests hormone replacement therapy (HRT) for severe vasomotor
symptoms. What is the recommendation?
A) HRT is contraindicated in BRCA1 carriers
B) Short-term HRT until natural menopause age (51) is safe and does not increase breast cancer risk
C) Only vaginal estrogen is allowed
D) HRT increases ovarian cancer risk
Correct Answer: B
*Rationale: Short-term HRT after BSO in BRCA1 carriers is safe and does not negate the breast cancer risk reduction
from BSO.*
Question 11
A 28-year-old man presents with tall stature, gynecomastia, small firm testes, and azoospermia. FSH is 25 IU/L
(elevated). What is the most likely karyotype?
A) 47,XXY
B) 47,XYY
C) 46,XX
D) 45,X/46,XY
Correct Answer: A
, Rationale: Klinefelter syndrome (47,XXY) presents with hypergonadotropic hypogonadism, small
testes, gynecomastia, and infertility.
Question 12
A patient with a CYP2C19 poor metabolizer phenotype (*2/*2) is prescribed clopidogrel after drug-eluting stent
placement. What is the expected clinical outcome?
A) Normal antiplatelet effect
B) Reduced active metabolite formation, increased risk of stent thrombosis
C) Increased bleeding risk
D) Enhanced platelet inhibition
Correct Answer: B
*Rationale: CYP2C19 poor metabolizers cannot convert clopidogrel to its active metabolite, leading to high on-
treatment platelet reactivity and increased thrombotic risk.*
Question 13
A 32-year-old woman with a BRCA1 pathogenic variant is 10 weeks pregnant. She requests prenatal diagnosis for the
familial variant. What is the earliest gestational age for chorionic villus sampling (CVS)?
A) 6 weeks
B) 10-13 weeks
C) 15 weeks
D) 18 weeks
Correct Answer: B
*Rationale: CVS is performed at 10-13 weeks gestation. Amniocentesis is performed at 15-20 weeks.*
Question 14
A 6-month-old infant presents with progressive macrocephaly, irritability, loss of developmental milestones, and
cherry-red spots on macula. Enzyme assay shows hexosaminidase A deficiency. What is the inheritance pattern?
A) Autosomal dominant
B) Autosomal recessive
C) X-linked dominant
D) Mitochondrial
Correct Answer: B
Rationale: Tay-Sachs disease (HEXA deficiency) is autosomal recessive, most common in Ashkenazi
Jewish population.
Question 15
A 45-year-old woman with Lynch syndrome (MSH2 pathogenic variant) undergoes annual colonoscopy. A 5 mm
sessile serrated polyp is removed. What is the recommended surveillance interval?
A) 1 year
B) 3 years
C) 5 years
D) 10 years
