Genetics Nursing Certification Examination on Hereditar
Assessment, Genetic Testing, and Counseling Services
2026
Genetics Nursing Certification Examination
Hereditary Risk Assessment, Genetic Testing, and Counseling Services
Difficulty: Advanced / Hard / Mixed
Target Audience: Advanced practice genetic nurses, certification candidates (e.g., GNCC)
Format: 150 multiple-choice questions, single best answer, with rationale
Question 1
A 35-year-old woman with a strong family history of breast cancer (mother at age 38, maternal aunt at age 42) tests
negative for a pathogenic *BRCA1/2* variant on comprehensive sequencing. Her mother’s tumor showed loss of
heterozygosity at BRCA1 but no germline variant. What is the most appropriate next step?
A) Reassure the patient that hereditary cancer is excluded
B) Recommend multigene panel testing (e.g., PALB2, CHEK2, ATM)
C) Proceed with bilateral mastectomy without further testing
D) Order *BRCA1/2* duplication/deletion analysis
Correct Answer: B
*Rationale: Strong family history of early-onset breast cancer with negative BRCA1/2 sequencing warrants multigene
panel testing to identify moderate- and high-risk genes not covered by single-gene testing.*
Question 2
A 28-year-old asymptomatic man undergoes predictive testing for Huntington disease because his father is affected.
His CAG repeat length in HTT is 42. What is the most accurate counseling regarding penetrance?
A) He will definitely develop symptoms before age 50
B) He has a 100% lifetime risk of developing Huntington disease, with variable age of onset
C) He has reduced penetrance and may never develop symptoms
D) He is a carrier but will remain asymptomatic
Correct Answer: B
Rationale: CAG ≥40 repeats is fully penetrant for Huntington disease, though age of onset is variable
and inversely correlated with repeat length.
Question 3
A 55-year-old woman of Ashkenazi Jewish descent is diagnosed with high-grade serous ovarian cancer. She has no
family history of breast or ovarian cancer. Genetic testing reveals a BRCA1 c.68_69delAG (185delAG) variant. What is
the most likely explanation for the absence of family history?
A) The variant is de novo
B) Incomplete penetrance and small family size
,C) The variant is a benign polymorphism
D) Maternal imprinting silenced the variant
Correct Answer: B
*Rationale: BRCA1/2 pathogenic variants have incomplete penetrance; family history may be absent due to small
family size, male carriers, or young unaffected relatives.*
Question 4
A patient with a pathogenic LDLR variant (familial hypercholesterolemia) has an LDL cholesterol of 190 mg/dL on
atorvastatin 40 mg. His 10-year-old son has an LDL of 210 mg/dL. What is the most appropriate management for the
son?
A) Initiate statin therapy immediately
B) Begin ezetimibe monotherapy
C) Lifestyle modification only until age 18
D) PCSK9 inhibitor as first-line
Correct Answer: A
*Rationale: HeFH in children with LDL ≥190 mg/dL or ≥160 mg/dL with family history of early CVD warrants statin
therapy starting at age 8-10 per AAP guidelines.*
Question 5
A 30-year-old woman with a BRCA1 pathogenic variant undergoes annual breast MRI. A new 1.2 cm enhancing mass
with irregular margins is noted. Core needle biopsy shows invasive ductal carcinoma, ER/PR negative, HER2 negative.
What is the most appropriate neoadjuvant therapy?
A) Tamoxifen
B) PARP inhibitor monotherapy
C) Platinum-based chemotherapy
D) Trastuzumab
Correct Answer: C
*Rationale: Triple-negative breast cancer in BRCA1 carriers is highly sensitive to platinum agents (cisplatin/carboplatin)
and PARP inhibitors, but neoadjuvant platinum-based chemotherapy is standard.*
Question 6
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. They are planning another pregnancy. Which test can be performed on maternal blood to
determine fetal SMN1 copy number noninvasively?
A) Cell-free fetal DNA sequencing for SMN1 dosage
B) Maternal serum AFP
C) Quad screen
D) First-trimester nuchal translucency
Correct Answer: A
Rationale: Noninvasive prenatal testing (NIPS) for SMA using relative haplotype dosage analysis or
digital PCR is available and can detect fetal SMN1 deletions.
,Question 7
A 45-year-old man with hereditary hemochromatosis (homozygous C282Y) has ferritin 1200 ng/mL and transferrin
saturation 85%. He has no diabetes, arthritis, or liver enzyme elevation. What is the most appropriate next step?
A) Liver biopsy
B) Phlebotomy weekly until ferritin <50 ng/mL
C) MRI liver iron quantification
D) Observation with annual ferritin
Correct Answer: B
*Rationale: Phlebotomy is indicated for ferritin >300 ng/mL in men regardless of symptoms to prevent iron-related
organ damage.*
Question 8
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 of this
disorder?
A) Autosomal dominant
B) Autosomal recessive
C) X-linked dominant
D) Mitochondrial
Correct Answer: B
Rationale: Tay-Sachs disease (hexosaminidase A deficiency, HEXA gene) is autosomal recessive,
common in Ashkenazi Jewish population.
Question 9
A 50-year-old woman with Lynch syndrome (MSH2 pathogenic variant) undergoes annual colonoscopy. A 6 mm sessile
serrated polyp is removed. What is the recommended surveillance interval?
A) 1 year
B) 3 years
C) 5 years
D) 10 years
Correct Answer: A
Rationale: Lynch syndrome patients with any polyp (including serrated) return to annual colonoscopy
due to accelerated carcinogenesis.
Question 10
A 32-year-old woman with a BRCA2 pathogenic variant and a strong family history of pancreatic cancer (father at age
50) asks about pancreatic cancer screening. Which imaging modality is recommended?
A) Annual CT abdomen
B) Annual EUS or MRI/MRCP starting at age 50 or 10 years before youngest family case
C) CA19-9 annually
, D) No screening recommended
Correct Answer: B
*Rationale: NCCN recommends pancreatic cancer screening with EUS or MRI in high-risk individuals (BRCA2 with family
history of pancreatic cancer) starting at age 50 or 10 years before earliest family case.*
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 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 breast cancer risk reduction from
BSO.*
Question 14
A 55-year-old man with hereditary ATTR amyloidosis (Val30Met) presents with progressive peripheral neuropathy,
Assessment, Genetic Testing, and Counseling Services
2026
Genetics Nursing Certification Examination
Hereditary Risk Assessment, Genetic Testing, and Counseling Services
Difficulty: Advanced / Hard / Mixed
Target Audience: Advanced practice genetic nurses, certification candidates (e.g., GNCC)
Format: 150 multiple-choice questions, single best answer, with rationale
Question 1
A 35-year-old woman with a strong family history of breast cancer (mother at age 38, maternal aunt at age 42) tests
negative for a pathogenic *BRCA1/2* variant on comprehensive sequencing. Her mother’s tumor showed loss of
heterozygosity at BRCA1 but no germline variant. What is the most appropriate next step?
A) Reassure the patient that hereditary cancer is excluded
B) Recommend multigene panel testing (e.g., PALB2, CHEK2, ATM)
C) Proceed with bilateral mastectomy without further testing
D) Order *BRCA1/2* duplication/deletion analysis
Correct Answer: B
*Rationale: Strong family history of early-onset breast cancer with negative BRCA1/2 sequencing warrants multigene
panel testing to identify moderate- and high-risk genes not covered by single-gene testing.*
Question 2
A 28-year-old asymptomatic man undergoes predictive testing for Huntington disease because his father is affected.
His CAG repeat length in HTT is 42. What is the most accurate counseling regarding penetrance?
A) He will definitely develop symptoms before age 50
B) He has a 100% lifetime risk of developing Huntington disease, with variable age of onset
C) He has reduced penetrance and may never develop symptoms
D) He is a carrier but will remain asymptomatic
Correct Answer: B
Rationale: CAG ≥40 repeats is fully penetrant for Huntington disease, though age of onset is variable
and inversely correlated with repeat length.
Question 3
A 55-year-old woman of Ashkenazi Jewish descent is diagnosed with high-grade serous ovarian cancer. She has no
family history of breast or ovarian cancer. Genetic testing reveals a BRCA1 c.68_69delAG (185delAG) variant. What is
the most likely explanation for the absence of family history?
A) The variant is de novo
B) Incomplete penetrance and small family size
,C) The variant is a benign polymorphism
D) Maternal imprinting silenced the variant
Correct Answer: B
*Rationale: BRCA1/2 pathogenic variants have incomplete penetrance; family history may be absent due to small
family size, male carriers, or young unaffected relatives.*
Question 4
A patient with a pathogenic LDLR variant (familial hypercholesterolemia) has an LDL cholesterol of 190 mg/dL on
atorvastatin 40 mg. His 10-year-old son has an LDL of 210 mg/dL. What is the most appropriate management for the
son?
A) Initiate statin therapy immediately
B) Begin ezetimibe monotherapy
C) Lifestyle modification only until age 18
D) PCSK9 inhibitor as first-line
Correct Answer: A
*Rationale: HeFH in children with LDL ≥190 mg/dL or ≥160 mg/dL with family history of early CVD warrants statin
therapy starting at age 8-10 per AAP guidelines.*
Question 5
A 30-year-old woman with a BRCA1 pathogenic variant undergoes annual breast MRI. A new 1.2 cm enhancing mass
with irregular margins is noted. Core needle biopsy shows invasive ductal carcinoma, ER/PR negative, HER2 negative.
What is the most appropriate neoadjuvant therapy?
A) Tamoxifen
B) PARP inhibitor monotherapy
C) Platinum-based chemotherapy
D) Trastuzumab
Correct Answer: C
*Rationale: Triple-negative breast cancer in BRCA1 carriers is highly sensitive to platinum agents (cisplatin/carboplatin)
and PARP inhibitors, but neoadjuvant platinum-based chemotherapy is standard.*
Question 6
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. They are planning another pregnancy. Which test can be performed on maternal blood to
determine fetal SMN1 copy number noninvasively?
A) Cell-free fetal DNA sequencing for SMN1 dosage
B) Maternal serum AFP
C) Quad screen
D) First-trimester nuchal translucency
Correct Answer: A
Rationale: Noninvasive prenatal testing (NIPS) for SMA using relative haplotype dosage analysis or
digital PCR is available and can detect fetal SMN1 deletions.
,Question 7
A 45-year-old man with hereditary hemochromatosis (homozygous C282Y) has ferritin 1200 ng/mL and transferrin
saturation 85%. He has no diabetes, arthritis, or liver enzyme elevation. What is the most appropriate next step?
A) Liver biopsy
B) Phlebotomy weekly until ferritin <50 ng/mL
C) MRI liver iron quantification
D) Observation with annual ferritin
Correct Answer: B
*Rationale: Phlebotomy is indicated for ferritin >300 ng/mL in men regardless of symptoms to prevent iron-related
organ damage.*
Question 8
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 of this
disorder?
A) Autosomal dominant
B) Autosomal recessive
C) X-linked dominant
D) Mitochondrial
Correct Answer: B
Rationale: Tay-Sachs disease (hexosaminidase A deficiency, HEXA gene) is autosomal recessive,
common in Ashkenazi Jewish population.
Question 9
A 50-year-old woman with Lynch syndrome (MSH2 pathogenic variant) undergoes annual colonoscopy. A 6 mm sessile
serrated polyp is removed. What is the recommended surveillance interval?
A) 1 year
B) 3 years
C) 5 years
D) 10 years
Correct Answer: A
Rationale: Lynch syndrome patients with any polyp (including serrated) return to annual colonoscopy
due to accelerated carcinogenesis.
Question 10
A 32-year-old woman with a BRCA2 pathogenic variant and a strong family history of pancreatic cancer (father at age
50) asks about pancreatic cancer screening. Which imaging modality is recommended?
A) Annual CT abdomen
B) Annual EUS or MRI/MRCP starting at age 50 or 10 years before youngest family case
C) CA19-9 annually
, D) No screening recommended
Correct Answer: B
*Rationale: NCCN recommends pancreatic cancer screening with EUS or MRI in high-risk individuals (BRCA2 with family
history of pancreatic cancer) starting at age 50 or 10 years before earliest family case.*
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 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 breast cancer risk reduction from
BSO.*
Question 14
A 55-year-old man with hereditary ATTR amyloidosis (Val30Met) presents with progressive peripheral neuropathy,
