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Question 1/101/10
Cytogenomic analysis and chromosomal abnormalities
Cytogenomic analysis and chromosomal abnormalities
Cytogenomic analysis and chromosomal abnormalities
A child with multiple congenital anomalies has a normal chromosomal microarray result. The clinical team strongly suspects a balanced reciprocal translocation disrupting a dosage-sensitive developmental gene. Which follow-up test is most appropriate to detect this type of abnormality?
Select the answer:Select the answer
1 correct answer
A.
G-banded chromosome analysis, with reflex targeted FISH if needed
B.
SNP chromosomal microarray with a lower reporting threshold
C.
Methylation-specific MLPA
D.
Fragile X CGG repeat analysis
Balanced reciprocal translocations usually do not cause copy-number gain or loss and are often not detected by chromosomal microarray. G-banded karyotyping can identify balanced rearrangements, and targeted FISH can further characterize breakpoints. A lower microarray threshold would still not reliably detect balanced events. Methylation-specific MLPA and Fragile X testing evaluate different molecular mechanisms.
Right Answer: A
Quiz
Question 2/102/10
Cancer genetics and somatic variant interpretation
Cancer genetics and somatic variant interpretation
Cancer genetics and somatic variant interpretation
Under AMP/ASCO/CAP somatic variant interpretation guidelines, which result is best classified as a Tier I variant?
Select the answer:Select the answer
1 correct answer
A.
EGFR p.L858R in lung adenocarcinoma, associated with an FDA-approved targeted therapy in that tumor type
B.
A synonymous TP53 variant with no known functional effect
C.
A missense variant in a cancer gene reported only as a variant of uncertain significance
D.
A germline benign polymorphism detected in tumor-only sequencing
Tier I variants have strong clinical significance, such as variants linked to FDA-approved therapies in the same tumor type. EGFR p.L858R in lung adenocarcinoma is a classic actionable Tier I alteration. Synonymous benign or uncertain variants are not Tier I, and benign germline polymorphisms should not be treated as clinically significant somatic findings.
Right Answer: A
Quiz
Question 3/103/10
Laboratory quality assurance, validation, and regulatory compliance
Laboratory quality assurance, validation, and regulatory compliance
Laboratory quality assurance, validation, and regulatory compliance
A clinical laboratory validates a new NGS panel for inherited disease testing. Which parameter must be established as part of analytical validation?
Select the answer:Select the answer
1 correct answer
A.
Analytical sensitivity, analytical specificity, accuracy, precision/reproducibility, reportable range, and limitations
B.
The prevalence of every disease included on the panel in the general population
C.
The clinical penetrance of every variant that may be detected
D.
The reimbursement rate for each gene on the panel
Analytical validation establishes how well the assay detects the intended variant types within the defined reportable range, including sensitivity, specificity, accuracy, precision/reproducibility, and limitations. Disease prevalence, penetrance of every possible variant, and reimbursement are not core analytical validation parameters.
Right Answer: A
Quiz
Question 4/104/10
Prenatal, postnatal, and reproductive genetic testing
Prenatal, postnatal, and reproductive genetic testing
Prenatal, postnatal, and reproductive genetic testing
A pregnant patient has a high-risk cell-free DNA screening result for trisomy 21. Ultrasound is normal. What is the most appropriate counseling point?
Select the answer:Select the answer
1 correct answer
A.
The result is a screening result and should be confirmed with diagnostic testing such as CVS or amniocentesis before irreversible clinical decisions
B.
The fetus is definitively affected because cell-free DNA testing has 100% positive predictive value
C.
No further testing is useful because ultrasound is normal
D.
Maternal karyotyping is the only appropriate confirmatory test
Cell-free DNA screening has high sensitivity and specificity for trisomy 21 but is still a screening test; positive predictive value varies with prior risk and prevalence. Diagnostic confirmation by CVS or amniocentesis is recommended before irreversible decisions. A normal ultrasound does not exclude trisomy 21, and maternal karyotyping alone does not confirm fetal status.
Right Answer: A
Quiz
Question 5/105/10
Copy number variant detection and interpretation
Copy number variant detection and interpretation
Copy number variant detection and interpretation
A chromosomal microarray identifies a 1.5 Mb de novo deletion that fully overlaps a well-established recurrent microdeletion syndrome region with known haploinsufficiency. According to ACMG/ClinGen CNV interpretation principles, what is the most appropriate classification?
Select the answer:Select the answer
1 correct answer
A.
Pathogenic
B.
Likely benign
C.
Benign because it is de novo
D.
Variant of uncertain significance because all CNVs require parental inheritance to be classified
A de novo deletion overlapping a known dosage-sensitive recurrent microdeletion syndrome region is strong evidence for pathogenicity. De novo status supports, rather than argues against, pathogenicity. Parental studies are helpful but not required for classification when sufficient established evidence exists.
Right Answer: A
Quiz
Question 6/106/10
Pharmacogenomics and clinical utility
Pharmacogenomics and clinical utility
Pharmacogenomics and clinical utility
A patient with acute lymphoblastic leukemia is found to have homozygous TPMT deficiency before starting thiopurine therapy. Which initial management is most appropriate?
Select the answer:Select the answer
1 correct answer
A.
Use full-dose mercaptopurine because genetic findings do not affect thiopurines
B.
Start with a substantially reduced thiopurine dose and monitor closely for myelosuppression
C.
Avoid all future chemotherapy because TPMT deficiency contraindicates cancer treatment
D.
Increase the dose if nausea occurs because this reflects underexposure
TPMT deficiency markedly increases risk of thiopurine toxicity. Clinical utility includes dose reduction and close monitoring rather than standard dosing.
Right Answer: B
Quiz
Question 7/107/10
Ethical, legal, and professional issues in genomic medicine
Ethical, legal, and professional issues in genomic medicine
Ethical, legal, and professional issues in genomic medicine
A patient undergoing germline testing asks whether results could affect eligibility for life insurance. The best response is to explain that:
Select the answer:Select the answer
1 correct answer
A.
genetic information is always fully protected from every insurer
B.
protections vary by jurisdiction and often differ for health, life, disability, and long-term care insurance
C.
the laboratory can erase all risk once the report is finalized
D.
insurance companies may only request results if the test is positive
Legal protections for genetic information are not uniform across all insurance products. In many settings, health insurance protections are stronger than those for life, disability, or long-term care insurance.
Right Answer: B
Quiz
Question 8/108/10
Test reporting, clinical correlation, and genetic counseling principles
Test reporting, clinical correlation, and genetic counseling principles
Test reporting, clinical correlation, and genetic counseling principles
A report for a hereditary cancer panel identifies a BRCA1 missense change classified as likely pathogenic. Which statement is most appropriate for the final interpretation section?
Select the answer:Select the answer
1 correct answer
A.
The variant is definitively causal for the patient's cancer
B.
The variant likely contributes to disease risk, but clinical correlation is required
C.
The variant should be treated as benign until proven otherwise
D.
The result rules out a hereditary cancer predisposition
Likely pathogenic variants are generally considered clinically relevant, but the report should avoid overstating certainty and should emphasize correlation with phenotype and family history.
Right Answer: B
Quiz
Question 9/109/10
Population genetics, inheritance patterns, and risk assessment
Population genetics, inheritance patterns, and risk assessment
Population genetics, inheritance patterns, and risk assessment
In a large population, a recessive disease allele has a frequency of 0.02. Assuming Hardy-Weinberg equilibrium, what is the expected carrier frequency?
Select the answer:Select the answer
1 correct answer
A.
0.0004
B.
0.0392
C.
0.96
D.
0.98
Carrier frequency is 2pq. With p = 0.98 and q = 0.02, 2pq = 0.0392.
Right Answer: B
Quiz
Question 10/1010/10
Genomic databases, bioinformatics, and annotation tools
Genomic databases, bioinformatics, and annotation tools
Genomic databases, bioinformatics, and annotation tools
A clinical laboratory needs a resource that curates human gene-disease relationships and provides standardized gene symbols. Which database is most appropriate?
Select the answer:Select the answer
1 correct answer
A.
ClinVar
B.
OMIM
C.
HGNC
D.
dbSNP
HGNC standardizes human gene nomenclature and approved gene symbols.
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Quiz name:LGG: ABMGG Laboratory Genetics and Genomics (LGG)
Total number of questions:476
Number of questions for the test:50
Pass score:80%
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