Medical Genetics & Genomic Knowledge Flashcards

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

Answer: Confined placental mosaicism

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

A compound heterozygote is an individual who has:

Answer: Two different pathogenic alleles at the same locus

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

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

Answer: Variant of uncertain significance

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

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

Answer: 50%

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

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

Answer: 39-44%

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

Huntington disease shows full penetrance when the CAG repeat count in HTT is at least:

Answer: 40

Alleles with 40 or more CAG repeats are fully penetrant, while 36-39 repeats show reduced penetrance.

How does DNA methylation at CpG islands in a gene promoter typically affect gene expression?

Answer: It represses transcription

Promoter CpG methylation generally silences transcription, as seen in imprinting and X inactivation.