eBook: WGS for Rare Disease Diagnosis
Impact of WGS to Clinical Management
Performance, Utility, and Implementation of WGS in a Clinical Setting


Genomics in Medicine: Educational App

On-demand educational courses that support the clinical use of genomic sequencing in pediatric care. Developed by a faculty of global experts in genomic sequencing, the courses are designed for HCPs interested reliable information to support implementation genomic sequencing into practice.

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Online Course: Clinical Sequencing in Rare Disease

This course offers an overview of pediatric rare disease, available testing options, and clinical implementation of genomic sequencing. It may be relevant to laboratory providers, healthcare providers, healthcare organizations, and others interested in a review of genomics in the rare disease population. This course was made possible through an educational grant from Illumina.

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Patient-centered Laboratory Utilization Guidance Services (PLUGS)

A laboratory stewardship collaborative with a mission to help patients to get the right test, help providers retrieve/understand the results correctly, and to improve the chances that the test is covered and paid for by a patient’s insurance plan

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Medical Policy: WGS for Rare Disease

Medical Policy: Rapid WGS for Rare Disease

Tools for Providers


Meta-analysis of the diagnostic and clinical utility of exome and genome sequencing in pediatric and adult patients with rare disease across diverse populations.
Chung CCY, Hue SPY, Ng NYT et al. Genet Med. 2023;

The aim of this meta-analysis was to compare the diagnostic and clinical utility of exome sequencing (ES) versus genome sequencing (GS) in patients with rare disease including papers published from 2012 to 2021. A total of 161 studies from 31 countries/regions reporting on 50,412 probands were evaluated after initial review. Half of the studies included exclusively pediatric probands, 43% were mixed pediatric and adult probands and 3% were exclusively adult. The remaining were unknown. The pooled diagnostic yield did not find a significant difference between ES and GS (38% vs. 34%; P=.01); however, the yield was higher in pediatric probands compared to adult probands. Clinical utility was reported in 62 publications noting that the proportion of patients experiencing a change in management was significantly greater following GS than ES (61% vs. 48%; p=0.07). Differences in diagnostic yield between ES and GS were also assessed with respect to trio vs. proband-only testing, clinical indication, rapid vs. non-rapid testing and number of variants of uncertain significance. To date, this is the most comprehensive comparison of diagnostic and clinical utility between ES and GS. Despite similar diagnostic yields between the two modalities, clinical utility following GS is significantly greater than that of ES.

The clinical utility of exome and genome sequencing across clinical indications: a systematic evidence review. Schick S, Mighton C, Uleryk E, Pechlivanoglou P, Bombard Y. Hum Genet.2021 Oct;140(10):1403-1416.doi: 10.1007/s00439-021-02331-x. Epub 2021 Aug 8.

Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability.
Malinowski J, Miller DT, Demmer L, et al. Genet Med. 2020 Jun;22(6):986-1004.

Genome-Wide Sequencing for Unexplained Developmental Disabilities or Multiple Congenital Anomalies: A Health Technology Assessment. Ontario Health Technology Assessment Series, 2020 Mar 6;20(11):1-178.

Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected diseases. Clark MM, Stark Z, Farnaes L, et al.. NPJ Genom Med. 2018 Jul 9;3:16. doi: 10.1038/s41525-018-0053-8.

Effect of Whole-Genome Sequencing on the Clinical Management of Acutely Ill Infants With Suspected Genetic Disease: A Randomized Clinical Trial. Krantz ID, Medne L, Weatherly JM, et al. JAMA Pediatr. 2021;175(12):1218-1226. doi:10.1001/jamapediatrics.2021.3496

Project baby bear: Rapid precision care incorporating rWGS in 5 California children’s hospitals demonstrates improved clinical outcomes and reduced costs of care. Dimmock D, Caylor S, Waldman B, et al. Am J Hum Genet. 2021 May 29S0002-9297(21)00192-0. doi: 10.1016/j.ajhg.2021.05.008. Epub ahead of print. PMID: 34089648.

A randomized controlled trial of the analytic and diagnostic performance of singleton and trio, rapid genome and exome sequencing in ill infants. Kingsmore SF, Cakici JA, Clark MM, et al. A J Hum Gen, 2019;105:1-15.

Rapid whole genome sequencing has clinical utility in the PICU. Sanford EF, Clark MM, Farnaes L, et al. PediatrCritCare Med. 2019 Jun 19. doi: 10.1097/PCC.0000000000002056.

The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants. Petrikin JE, Cakici JA, Clark MM, Willig LK, Sweeney NM, Farrow EG, Saunders CJ, Thiffault I, Miller NA, Zellmer L, Herd SM, Holmes AM, Batalov S, Veeraraghavan N, Smith LD, Dimmock DP, Leeder JS, Kingsmore SF. NPJ Genom Med. 2018 Feb 9;3:6. doi: 10.1038/s41525-018-0045-8.

Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients. Abdul-Husn NS, Marathe PN, Kelly NR, et al. Genet Med. 2023.

Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability. Lindstrand A, Ek M, Kvarnung M, Anderlid BM, et al. Genet Med. 2022 Nov;24(11):2296-2307. doi: 10.1016/j.gim.2022.07.022. Epub 2022 Sep 6. PMID: 36066546.

Genome sequencing demonstrates high diagnostic yield in children with undiagnosed global developmental delay/intellectual disability: A prospective study. Sun Y, Peng J, Liang D, et al. Hum Mutat. 2022 May;43(5):568-581.doi: 10.1002/humu.24347. Epub 2022 Mar 1.

100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care —Preliminary Report. 100,000 Genomes Project Pilot Investigators, Smedley D, Smith KR, et al. N Engl J Med. 2021 Nov 11;385(20):1868-1880.

Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients. Stranneheim H, Lagerstedt-Robinson K, Magnusson M, et al. Genome Med.2021 Mar 17;13(1):40.

Diagnostic yield and treatment impact of whole-genome sequencing in paediatric neurological disorders. Lee HF, Chi CS, Tsai CR. Dev Med Child Neurol. 2021 Aug;63(8):934-938.

Cost-effectiveness of exome and genome sequencing for children with rare and undiagnosed conditions. Lavelle TA, Feng X, Keisler M, et al. Genet Med. 2022 Jun;24(6):1349-1361. doi: 10.1016/j.gim.2022.03.005

Cost-effectiveness of genome sequencing for diagnosing patients with undiagnosed rare genetic diseases. Incerti D, Xu XM, Chou JW, Gonzaludo N, et al. Genet Med. 2022 Jan;24(1):109-118. doi: 10.1016/j.gim.2021.08.015

Project baby bear: Rapid precision care incorporating rWGS in 5 California children’s hospitals demonstrates improved clinical outcomes and reduced costs of care. Dimmock D, Caylor S, Waldman B, et al. Am J Hum Genet. 2021 May 29S0002-9297(21)00192-0. doi: 10.1016/j.ajhg.2021.05.008. Epub ahead of print. PMID: 34089648.

Estimating the burden and economic impact of pediatric genetic disease. Gonzaludo N, Belmont JW, Gainullin VG, Taft RJ. Genet Med. 2019. doi: 10.1038/s41436-019-0458-5. Epub ahead of print.

Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization. Farnaes L, Hildreth A, Sweeney NM, et al. NPJ Genom Med. 2018 Apr 4;3:10. doi: 10.1038/s41525- 018-0049-4.

Your Investigation with WGS