Session # 57

Low Variant Allele Fraction in Germline Genetic Testing Predicts Pathogenicity of NF1 Variants

Presenting Author: Shoji Ichikawa, PhD

Take home points: 

1. The NF1 gene is included in multigene panel testing for cancer predisposition, and low variant allele fraction (VAF) in NF1 variants is frequently observed in genomic DNA extracted from blood or saliva.
2. There are multiple biological and technical causes of low VAF associated with NF1 variants. One of the causes is thought to be clonal hematopoiesis, where the NF1 gene provides a selective advantage to hematopoietic stem cells when mutated.
3. We analyzed VAF of rare NF1 variants identified in germline genetic testing. Over 23% of likely pathogenic/pathogenic variants were detected at low VAF, whereas low VAF was observed with <1% of likely benign/benign variants.
4. Our data suggests that low VAF is significantly associated with NF1 pathogenic variants likely due to clonal hematopoiesis and can provide in vivo functional evidence to aid classification of NF1 variants.

• Authors: Shoji Ichikawa; Timothy Komala; Meghan Towne
• Conference: NF 2024
• Date: Saturday, Jun 22, 2024 3:30pm - 5:30pm