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Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system, EVIDENCE
Author(s) -
Seo Go Hun,
Kim Taeho,
Choi In Hee,
Park Jungyoung,
Lee Jungsul,
Kim Sehwan,
Won Dhonggun,
Oh Arum,
Lee Yena,
Choi Jeongmin,
Lee Hajeong,
Kang Hee Gyung,
Cho Hee Yeon,
Cho Min Hyun,
Kim Yoon Jeon,
Yoon Young Hee,
Eun BaikLin,
Desnick Robert J.,
Keum Changwon,
Lee Beom Hee
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13848
Subject(s) - proband , exome sequencing , genetic testing , prioritization , exome , medicine , phenotype , genetics , dna sequencing , medical genetics , bioinformatics , mutation , biology , gene , management science , economics
EVIDENCE, an automated variant prioritization system, has been developed to facilitate whole exome sequencing analyses. This study investigated the diagnostic yield of EVIDENCE in patients with suspected genetic disorders. DNA from 330 probands (age range, 0‐68 years) with suspected genetic disorders were subjected to whole exome sequencing. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments. EVIDENCE reported a total 228 variants in 200 (60.6%) of the 330 probands. The average number of organs involved per patient was 4.5 ± 5.0. After clinical reassessment and/or family member testing, 167 variants were identified in 141 probands (42.7%), including 105 novel variants. These variants were confirmed as being responsible for 121 genetic disorders. A total of 103 (61.7%) of the 167 variants in 95 patients were classified as pathogenic or probably to be pathogenic before, and 161 (96.4%) variants in 137 patients (41.5%) after, clinical assessment and/or family member testing. Factor associated with a variant being regarded as causative includes similar symptom scores of a gene variant to the phenotype of the patient. This new, automated variant interpretation system facilitated the diagnosis of various genetic diseases with a 42.7% diagnostic yield.