2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Diagnostic Yield of a Custom Targeted Genotyping Panel for Carrier Screening of >2,000 Samples: The Case Against Cystic Fibrosis-Only Testing

Diagnostic Yield of a Custom Targeted Genotyping Panel for Carrier Screening of >2,000 Samples: The Case Against Cystic Fibrosis-Only Testing

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Pdf Summary

The document describes the implementation and results of a targeted genotyping panel for carrier screening. The panel includes cystic fibrosis (CF), spinal muscular atrophy (SMA), and hemoglobinopathies, as well as other disorders. The objective of the study was to compare the diagnostic yield of CF-only testing to that of Tier 1 testing, which includes CF, SMA, and hemoglobinopathies.<br /><br />The results showed that the expanded panel greatly improved the clinical utility of CF testing by identifying ethnically agnostic variants, complex/compound variants, and multi-exon deletions. Incidental findings in CF-only screens were also observed and highlighted a significant proportion of unreported variants for Tier 1 disorders.<br /><br />The clinical significance of the incidental Tier 1 variants was explained. For example, individuals with alpha-thalassemia silent carrier may pass the deleted allele to the next generation, and those with Hb S variant "sickle cell trait" may develop sickling of hemoglobin under certain conditions and may pass the allele to the next generation.<br /><br />The overall diagnostic yield of the panel for CF was 12.4% compared to 25.2% for Tier 1 testing, and 35.0% when including the SMN1 "silent carrier" SNP. The diagnostic yield was further increased by including deletions in Tier 3 genes.<br /><br />The document also discusses the adoption of a tiered approach to carrier screening by the American College of Medical Genetics and Genomics (ACMG). The authors mention the challenges of insurance coverage for the larger Tier 3 panels and the continued demand for CF-only testing despite education efforts.<br /><br />In conclusion, the study demonstrates the improved clinical utility of a targeted genotyping panel for carrier screening. The results support the use of expanded panels that include CF, SMA, and hemoglobinopathies, as well as other disorders.

Asset Subtitle

Presenting Author - Nisha Kanwar, PhD; Co-Author - Jennifer Winters, BS; Co-Author - Amber M. McDonald, BS; Co-Author - Sean Harrington, BS; Co-Author - Rhonda K. Kuennen, BS; Co-Author - Sarah Thieke, BS; Co-Author - Linda Hasadsri, MD, PhD, FACMG;

Meta Tag

Genetic Testing

Genomic Methodologies

Variant Detection

Co-Author Jennifer Winters, BS

Co-Author Amber M. McDonald, BS

Co-Author Sean Harrington, BS

Co-Author Rhonda K. Kuennen, BS

Co-Author Sarah Thieke, BS

Co-Author Linda Hasadsri, MD, PhD, FACMG

Presenting Author Nisha Kanwar, PhD

Keywords

targeted genotyping panel

carrier screening

cystic fibrosis

spinal muscular atrophy

hemoglobinopathies

diagnostic yield

incidental findings

clinical significance

tiered approach

expanded panels