Kidney Week 2025 Early Program - Genetics in Clinical Nephrology-Genetics Basics: What Should I Know Before Ordering a Genetic Test?

Video Transcription

Video Summary

Daniella Delgaudio (University of Chicago Medicine) explains what clinicians should know before ordering genetic tests. She reviews the human genome (23 nuclear chromosome pairs plus mitochondrial DNA) and the Human Genome Project, noting the reference genome evolved from a mosaic of donors and has improved over time, culminating in a more complete reference in 2022. She emphasizes that genes can have multiple transcripts, so choosing a medically relevant “standard” transcript is important for consistent variant annotation and interpretation.<br /><br />She outlines disease-causing variant types: single-nucleotide variants (synonymous, missense, nonsense), small insertions/deletions (including frameshifts), canonical splice-site variants that disrupt RNA splicing, and copy number variants (exon/gene deletions/duplications). She summarizes ACMG/AMP five-tier classification (pathogenic to benign) and evidence used (population, computational, functional, segregation). Report outcomes include negative, positive, carrier, and VUS; VUSs should not guide decisions and may be reclassified. Finally, she reviews testing options—karyotype/microarray for chromosomal/CNV disorders, targeted tests or multigene panels for heterogeneous conditions, and exome/genome sequencing when prior testing is nondiagnostic.

Asset Subtitle

Daniela Del Gaudio

Keywords

genetic testing for clinicians

reference genome and Human Genome Project

transcript selection for variant annotation

pathogenic variant types (SNV indel splice CNV)

ACMG/AMP variant classification and evidence

exome genome sequencing vs karyotype microarray panels