2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Real-World Evidence Demonstrating Why Genome Sequencing Should Be Recommended as the First-Tier Genetic Test

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Genome sequencing (GS) has the potential to greatly improve diagnostic outcomes for individuals with suspected rare genetic diseases. A study was conducted to evaluate the diagnostic yield of GS as both a first-tier test and a follow-up test. The study analyzed 2100 clinical GS cases performed since 2017.<br /><br />The GS performed by the laboratory had several key features, including mean coverage of 40x throughout the entire genome, complete coverage of over 99% of the exome (including disease-associated genes), reliable detection of deletions, duplications, and structural rearrangements, analysis of the mitochondrial genome, and screening for repeat expansion disorders and Spinal Muscular Atrophy.<br /><br />The diagnostic outcome of the GS cases was determined based on the association of reportable variants with the patient's phenotype and clinical manifestations. The cases were classified into four categories: definitive diagnostic, assumed diagnostic, cases with variants of uncertain significance (VUS), and cases with apparently negative results.<br /><br />The study found that GS as a first-tier test had a high diagnostic yield, especially in cases where previous genetic tests were inconclusive. It was recommended that GS be recommended as the first-tier genetic test to shorten the diagnostic odyssey for patients with suspected rare genetic diseases.<br /><br />This study presented the largest dataset of GS cases from a clinically heterogeneous cohort in a single clinical laboratory. It demonstrated the clinical utility of GS in diagnosing rare genetic diseases and highlighted the importance of considering GS for patients with inconclusive genetic test results.<br /><br />Overall, the study provided real-world evidence supporting the recommendation of GS as the first-tier genetic test, offering hope for individuals seeking a diagnosis for their rare genetic disease.

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Presenting Author - Fen Guo, PhD, FACMG, FCCMG; Co-Author - Ruby Liu, PhD, CGC; Co-Author - Yinghong Pan, PhD; Co-Author - Christin D. Collins, PhD; Co-Author - Lora H. Bean, PhD; Co-Author - Babi Ramesh Reddy Nallamilli, PhD; Co-Author - Naga M. Guruju, PhD, FACMG; Co-Author - Xiangwen Chen-Deutsch, PhD; Co-Author - Rizwan Yousaf, PhD; Co-Author - Ephrem Chin, MBA, BTech(Hon), MB(ASCP) CM, QLC CM, CGMBS; Co-Author - Cristina da Silva, MS; Co-Author - Abhinav Mathur, MS; Co-Author - Zeqiang Ma, PhD; Co-Author - Jorune Balciuniene, PhD; Co-Author - Madhuri Hegde, PhD;

Meta Tag

Exome sequencing

Genetic Testing

Genome sequencing

NextGen Sequencing

Policy Issues

Co-Author Ruby Liu, PhD, CGC

Co-Author Yinghong Pan, PhD

Co-Author Christin D. Collins, PhD

Co-Author Lora H. Bean, PhD

Co-Author Babi Ramesh Reddy Nallamilli, PhD

Co-Author Naga M. Guruju, PhD, FACMG

Co-Author Xiangwen Chen-Deutsch, PhD

Co-Author Rizwan Yousaf, PhD

Co-Author Ephrem Chin, MBA, BTech(Hon), MB(ASCP) CM, QLC CM, CGMBS

Co-Author Cristina da Silva, MS

Co-Author Abhinav Mathur, MS

Co-Author Zeqiang Ma, PhD

Co-Author Jorune Balciuniene, PhD

Co-Author Madhuri Hegde, PhD

Presenting Author Fen Guo, PhD, FACMG, FCCMG

Keywords

genome sequencing

diagnostic outcomes

rare genetic diseases

first-tier test

clinical GS cases

mean coverage

exome

deletions

duplications

clinical utility