ABGC Certification Examination (CGC) cheat sheet

Informed consent for genetic testing requires documenting the test's purpose, limitations, possible results (including variants of uncertain significance), and implications for relatives.

Pretest counseling elements: reason for referral, family and medical history, test options, benefits/risks/limitations, cost and coverage, and plan for results disclosure.

Autosomal recessive recurrence risk between carrier parents is 25% per pregnancy regardless of prior affected children; prior outcomes do not alter subsequent independent risk.

Autosomal dominant recurrence risk from an affected heterozygous parent is 50% per pregnancy; risk applies to each pregnancy independently.

X-linked recessive: carrier mother transmits the allele to 50% of sons (affected) and 50% of daughters (carriers); affected fathers pass the allele to all daughters and no sons.

Bayesian risk calculation updates prior probability with conditional information (e.g., negative test result, unaffected age) to yield a posterior probability.

Results disclosure should address variant classification (pathogenic, likely pathogenic, VUS, likely benign, benign) and specify that VUS results are not clinically actionable.

Duty to warn/recontact relatives is handled through patient-mediated disclosure; counselors provide family letters and document patient preferences about relative notification.

Documentation should record pedigree findings, risk figures communicated, decisions made, and referrals, supporting continuity and medico-legal defensibility.

Pedigree symbols: square = male, circle = female, filled = affected, half-filled = carrier, diagonal line = deceased, double line = consanguinity, arrow = proband.

Hardy-Weinberg: carrier frequency for an autosomal recessive condition approximates 2√q when q (disease allele frequency) is small and the population is in equilibrium.

Aneuploidy risk rises with maternal age; trisomy 21 risk is commonly quoted as approximately 1 in 1,500 at age 20, 1 in 270 at age 35, and 1 in 100 at age 40.

Prenatal screening vs diagnosis: maternal serum screening and cell-free DNA are screening tests with false positives/negatives; chorionic villus sampling and amniocentesis are diagnostic.

Mitochondrial inheritance: transmitted through the maternal line; affected males do not transmit, and heteroplasmy produces variable expressivity among maternal relatives.

Imprinting disorders (e.g., Prader-Willi, Angelman) depend on parent of origin of the deleted or uniparental region on chromosome 15q11-q13.

Trisomy 21 cytogenetic forms: about 95% free trisomy 21, about 3-4% Robertsonian translocation (often 14;21), and 1-2% mosaicism.

Cystic fibrosis is autosomal recessive with a carrier frequency of about 1 in 25 in people of Northern European ancestry, yielding roughly 1 in 2,500 affected births.

Genetic testing modalities: karyotype detects structural and numerical changes; FISH targets specific loci; chromosomal microarray detects copy-number variants; sequencing detects point variants and small indels.