2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Diagnostic Yield and Copy Number Findings from 500 Clinical Genome Sequencing Cases

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The Greenwood Genetic Center conducted a study on the diagnostic yield and copy number findings from the first 500 clinical genome sequencing (WGS) cases. The study aimed to determine the effectiveness of WGS in identifying sequence alterations (SNVs) and copy number variants (CNVs) simultaneously. Blood-derived patient DNA samples were analyzed using short read WGS, and sequence alignment and variant analysis were performed using specific software. CNV analysis was conducted using NxClinical software.<br /><br />The study included pediatric patients, with a majority of cases involving one or both parents in the analysis. The results showed that 62% of the WGS cases had reported findings, including pathogenic and likely pathogenic alterations as well as variants of uncertain clinical significance. Furthermore, 6% of cases had both reported sequence and copy number findings.<br /><br />The study concluded that WGS was highly effective in identifying both SNVs and CNVs. Most of the identified CNVs would have been detected using traditional array-based methods, although some smaller exon-level CNVs were missed. The inclusion of parental samples improved variant classification and reduced the number of CNVs of uncertain significance. However, the study also noted limitations in detecting balanced rearrangements, low-level mosaicism, and CNVs in a specific size range.<br /><br />In summary, the study demonstrated the diagnostic yield of WGS in a clinical setting and highlighted the importance of incorporating both SNV and CNV analysis. The findings have implications for improving the genetic testing and diagnosis of patients with various phenotypes.

Asset Subtitle

Presenting Author - Kameryn M. Butler, PhD, FACMG; Co-Author - Benjamin A. Hilton, PhD; Co-Author - Timothy Fee, PhD; Co-Author - Barbara R. DuPont, PhD, FACMG;

Meta Tag

Chromosomal Abnormalities

Cytogenetics

Genetic Testing

Genome sequencing

Intellectual disability

Microarray

NextGen Sequencing

Variant Detection

Co-Author Benjamin A. Hilton, PhD

Co-Author Timothy Fee, PhD

Co-Author Barbara R. DuPont, PhD, FACMG

Presenting Author Kameryn M. Butler, PhD, FACMG

Keywords

Greenwood Genetic Center

clinical genome sequencing

diagnostic yield

copy number findings

sequence alterations

SNVs

copy number variants

CNVs

pediatric patients

NxClinical software