RT Journal Article
SR Electronic
T1 Pilot study of EVIDENCE: High diagnostic yield and clinical utility of whole exome sequencing using an automated interpretation system for patients with suspected genetic disorders
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 628438
DO 10.1101/628438
A1 Go Hun Seo
A1 Taeho Kim
A1 Jung-young Park
A1 Jungsul Lee
A1 Sehwan Kim
A1 Dhong-gun Won
A1 Arum Oh
A1 Yena Lee
A1 In Hee Choi
A1 Jeongmin Choi
A1 Hajeong Lee
A1 Hee Gyung Kang
A1 Hee Yeon Cho
A1 Min Hyun Cho
A1 Yoon Jeon Kim
A1 Young Hee Yoon
A1 Baik-Lin Eun
A1 Robert J Desnick
A1 Changwon Keum
A1 Beom Hee Lee
YR 2019
UL http://biorxiv.org/content/early/2019/11/15/628438.abstract
AB Purpose EVIDENCE, an automated interpretation system, has been developed to facilitate the entire process of whole exome sequencing (WES) analyses. This study investigated the diagnostic yield of EVIDENCE in patients suspected genetic disorders.Methods DNA from 330 probands (age range, 0–68 years) with suspected genetic disorders were subjected to WES. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments.Results The average number of overlapping organ categories per patient was 4.5 ± 5.0. EVIDENCE reported a total 244 variants in 215 (65.1%) of the 330 probands. After clinical reassessment and/or family member testing, 196 variants were identified in 171 probands (51.8%), including 115 novel variants. These variants were confirmed as being responsible for 146 genetic disorders. One hundred-seven (54.6%) of the 196 variants were categorized as pathogenic or likely pathogenic before, and 146 (74.6%) after, clinical assessment and/or family member testing. Factors associated with a variant being confirmed as causative include rules, such as PVS1, PS1, PM1, PM5, and PP5, and similar symptom scores between that variant and a patient’s phenotype.Conclusion This new, automated variant interpretation system facilitated the diagnosis of various genetic diseases with a 51% improvement in diagnostic yield.