TY - JOUR
T1 - Semiautomated approach focused on new genomic information results in time and effort-efficient reannotation of negative exome data
AU - Ferrer, Alejandro
AU - Duffy, Patrick
AU - Olson, Rory J.
AU - Meiners, Michael A.
AU - Schultz-Rogers, Laura
AU - Macke, Erica L.
AU - Safgren, Stephanie
AU - Morales-Rosado, Joel A.
AU - Cousin, Margot A.
AU - Oliver, Gavin R.
AU - Rider, David
AU - Williams, Megan
AU - Pichurin, Pavel N.
AU - Deyle, David R.
AU - Morava, Eva
AU - Gavrilova, Ralitza H.
AU - Dhamija, Radhika
AU - Wierenga, Klass J.
AU - Lanpher, Brendan C.
AU - Babovic-Vuksanovic, Dusica
AU - Kaiwar, Charu
AU - Vitek, Carolyn R.
AU - McAllister, Tammy M.
AU - Wick, Myra J.
AU - Schimmenti, Lisa A.
AU - Lazaridis, Konstantinos N.
AU - Vairo, Filippo Pinto e.
AU - Klee, Eric W.
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.
PY - 2024
Y1 - 2024
N2 - Most rare disease patients (75–50%) undergoing genomic sequencing remain unsolved, often due to lack of information about variants identified. Data review over time can leverage novel information regarding disease-causing variants and genes, increasing this diagnostic yield. However, time and resource constraints have limited reanalysis of genetic data in clinical laboratories setting. We developed RENEW, (REannotation of NEgative WES/WGS) an automated reannotation procedure that uses relevant new information in on-line genomic databases to enable rapid review of genomic findings. We tested RENEW in an unselected cohort of 1066 undiagnosed cases with a broad spectrum of phenotypes from the Mayo Clinic Center for Individualized Medicine using new information in ClinVar, HGMD and OMIM between the date of previous analysis/testing and April of 2022. 5741 variants prioritized by RENEW were rapidly reviewed by variant interpretation specialists. Mean analysis time was approximately 20 s per variant (32 h total time). Reviewed cases were classified as: 879 (93.0%) undiagnosed, 63 (6.6%) putatively diagnosed, and 4 (0.4%) definitively diagnosed. New strategies are needed to enable efficient review of genomic findings in unsolved cases. We report on a fast and practical approach to address this need and improve overall diagnostic success in patient testing through a recurrent reannotation process.
AB - Most rare disease patients (75–50%) undergoing genomic sequencing remain unsolved, often due to lack of information about variants identified. Data review over time can leverage novel information regarding disease-causing variants and genes, increasing this diagnostic yield. However, time and resource constraints have limited reanalysis of genetic data in clinical laboratories setting. We developed RENEW, (REannotation of NEgative WES/WGS) an automated reannotation procedure that uses relevant new information in on-line genomic databases to enable rapid review of genomic findings. We tested RENEW in an unselected cohort of 1066 undiagnosed cases with a broad spectrum of phenotypes from the Mayo Clinic Center for Individualized Medicine using new information in ClinVar, HGMD and OMIM between the date of previous analysis/testing and April of 2022. 5741 variants prioritized by RENEW were rapidly reviewed by variant interpretation specialists. Mean analysis time was approximately 20 s per variant (32 h total time). Reviewed cases were classified as: 879 (93.0%) undiagnosed, 63 (6.6%) putatively diagnosed, and 4 (0.4%) definitively diagnosed. New strategies are needed to enable efficient review of genomic findings in unsolved cases. We report on a fast and practical approach to address this need and improve overall diagnostic success in patient testing through a recurrent reannotation process.
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U2 - 10.1007/s00439-024-02664-3
DO - 10.1007/s00439-024-02664-3
M3 - Article
AN - SCOPUS:85189011743
SN - 0340-6717
JO - Human genetics
JF - Human genetics
ER -