CGC Medical Genetics & Genomic Knowledge 5

Question 1

What is the most common biological explanation for a false-positive cell-free DNA screen for a trisomy?

Accepted Answer

Confined placental mosaicism

Answer

cfDNA derives largely from placental trophoblast, so confined placental mosaicism can give a positive result with a normal fetal karyotype.

Question 2

A compound heterozygote is an individual who has:

Accepted Answer

Two different pathogenic alleles at the same locus

Answer

Compound heterozygotes carry two different mutant alleles at one locus, one on each homologous chromosome.

Question 3

How is a variant reported when available evidence is insufficient to classify it as pathogenic or benign?

Accepted Answer

Variant of uncertain significance

Answer

A VUS is the ACMG/AMP category for variants with conflicting or insufficient evidence.

Question 4

Approximately what proportion of neurofibromatosis type 1 cases arise from de novo mutations?

Accepted Answer

50%

Answer

About half of NF1 cases are de novo, reflecting the high mutation rate of the NF1 gene.

Question 5

What is the approximate lifetime risk of ovarian cancer for women with a BRCA1 pathogenic variant?

Accepted Answer

39-44%

Answer

BRCA1 carriers have about a 39-44% lifetime ovarian cancer risk, higher than for BRCA2 carriers at about 11-17%.

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