2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Reanalysis of Intronic Variants Reveals Novel Likely Pathogenic <em>DICER1</em> Splice Variant in Pleuropulmonary Blastoma Proband

Reanalysis of Intronic Variants Reveals Novel Likely Pathogenic DICER1 Splice Variant in Pleuropulmonary Blastoma Proband

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Pdf Summary

A study conducted by researchers from Baylor College of Medicine and the HudsonAlpha Institute for Biotechnology has identified a novel splice variant in the DICER1 gene that is likely to be pathogenic in a patient with Pleuropulmonary Blastoma (PPB). The study utilized publicly available data from ClinVar and analyzed germline exomes of pediatric cancer patients from the Texas KidsCanSeq (KCS) study.<br /><br />The researchers developed a pipeline to identify potential splice variants in DICER1 that may have been missed by clinical pipelines. They identified three prioritized variants with reciprocal splice loss and gain. Further investigation revealed that one of these variants, NM_177438.3(DICER1):c.5499G>A (p.Val1833=), was previously designated as likely benign but was found to disrupt splicing in the PPB patient.<br /><br />In addition to the novel splice variant, the study also highlighted a misinterpreted variant in two patients with DICER1 syndrome phenotypes. The variant, NM_177438.3(DICER1):c.2256+10G>C, was originally classified as likely benign but was found to be potentially pathogenic due to its proximity to the 5' splice site.<br /><br />This study emphasizes the importance of functional analysis and reclassification of genetic variants to enhance our understanding of disease mechanisms and improve clinical management. The findings contribute to the growing body of knowledge on DICER1 and its association with cancer predisposition syndromes.

Asset Subtitle

Presenting Author - Owen Hirschi, BS; Co-Author - Stephanie A. Felker, MS; Co-Author - Surya P. Rednam, MD; Co-Author - Kelly L. Vallance, MD, MPH; Co-Author - D. Williams Parsons, MD; Co-Author - Angshumoy Roy, MD, PhD; Co-Author - Gregory M. Cooper, PhD; Co-Author - Sharon E. Plon, MD,PhD, FACMG;

Meta Tag

Bioinformatics

Cancer Syndromes

Databases

Exome sequencing

Genetic Testing

Genome sequencing

NextGen Sequencing

Sequencing

Variant Detection

Co-Author Stephanie A. Felker, MS

Co-Author Surya P. Rednam, MD

Co-Author Kelly L. Vallance, MD, MPH

Co-Author D. Williams Parsons, MD

Co-Author Angshumoy Roy, MD, PhD

Co-Author Gregory M. Cooper, PhD

Co-Author Sharon E. Plon, MD,PhD, FACMG

Presenting Author Owen Hirschi, BS

Keywords

DICER1 gene

splice variant

pathogenic

Pleuropulmonary Blastoma

germline exomes

pediatric cancer patients

clinical pipelines

splicing disruption

DICER1 syndrome

genetic variants