2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Confirmation of complex events detected by NGS

Pdf Summary

The document discusses the challenges in characterizing and interpreting structural variants (SVs) detected by next-generation sequencing (NGS). It highlights that the random distribution of genes on capture-based NGS panels often makes it difficult to determine the copy state of genes adjacent to a copy number event. Therefore, additional methods such as chromosomal microarray (CMA) and multiplex-ligation dependent probe amplification (MLPA) are necessary to characterize the extent of the SVs.<br /><br />The document emphasizes the importance of using a well-rounded set of orthogonal methodologies for complete characterization and clinical interpretation of the range of variants detected by NGS. It states that as NGS technology improves, more variant types can be detected, but integrating and interpreting multiple variant types into one test is challenging within the existing testing frameworks.<br /><br />The document includes case studies where additional characterization was performed to determine the relevance and reportability of the detected variants. Examples include the characterization of transposable element insertions affecting sequencing coverage, the use of CMA to determine the extent of copy number calls in specific genes, and the use of MLPA to identify methylation patterns in genes associated with specific syndromes.<br /><br />The document also discusses the detection of mosaic complex structural events and splice variants. It describes how confirmation testing using various methods, such as Sanger sequencing and PCR, was performed to validate the presence of these variants.<br /><br />Overall, the document highlights the importance of additional characterization methods to accurately interpret and report the variants detected by NGS, particularly for complex structural variants and mosaic findings.

Asset Subtitle

Presenting Author - Lauren A. Choate, PhD; Co-Author - Amber M. McDonald, BS; Co-Author - Patrick A. Lundquist, BS; Co-Author - Francis Hoffman, BS; Co-Author - Angela M. Pickart, MS, CGC; Co-Author - Emily Lauer, MS, CGC; Co-Author - Sarah Thieke, BS; Co-Author - Rebecca Hofmeister, BS; Co-Author - Erik C. Thorland, PhD; Co-Author - Cherisse A. Marcou;

Meta Tag

Genetic Testing

Genomic Structure

NextGen Sequencing

Variant Detection

Co-Author Amber M. McDonald, BS

Co-Author Patrick A. Lundquist, BS

Co-Author Francis Hoffman, BS

Co-Author Angela M. Pickart, MS, CGC

Co-Author Emily Lauer, MS, CGC

Co-Author Sarah Thieke, BS

Co-Author Rebecca Hofmeister, BS

Co-Author Erik C. Thorland, PhD

Co-Author Cherisse A. Marcou

Presenting Author Lauren A. Choate, PhD

Keywords

structural variants

next-generation sequencing

copy number event

chromosomal microarray

multiplex-ligation dependent probe amplification

orthogonal methodologies

variant types

testing frameworks

transposable element insertions

mosaic complex structural events