Guidelines for NGS diagnostics Validation Critical steps ... fileAritmia AMC YES 47 targeted A...

Bert Bakker (LUMC), Bart Janssen (SXS) Milan Macek (Charles University, Prague)

Guidelines for NGS diagnostics Validation

Critical steps in the process

Project acronym: 3Gb-TESTProject full title: " Introducing diagnostic applications of ‘3Gb-testing’ in human genetics "Name of the coordinating person: E. Bakker, LeidenGrant agreement no: 602269September 2013- 2015

Bert Bakker (LUMC), Bart Janssen (SXS)

Research = Diagnostics

2005- 2010- 2013

2009-2012

http://www.eurogentest.org/.........../final_draft_02-12-2014_v2.pdf

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Guidelines

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Guidelines for NGS diagnostics

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TERMINOLOGY

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For diagnostic purpose, only genes with a known (i.e. published and confirmed) relationship between the abberant genotype and the pathology should be included in the analysis.

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‘Core gene’ list

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‘Scoring system’ for gene panel and exomes

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LIST centre

core NL (Yes/No)

core cente(Yes/No)

core (# genes)

Total #genes

Targeted/WES score

Avaragehorizontal coverage (20x depth) Implem.

CARDIOcardiomyopathy AMC YES YES 45 46targeted B Yescardiomyopathy Groningen YES YES 45 52 Yescardiomyopathy Maastricht YES YES 45 46 Yescardiomyopathy Rotterdam YES YES 47 47targeted Yescardiomyopathy Utrecht YES YES 45 69targeted B >99%; >95% Yes

Transduction dis. Utrecht YES YES 33 B >95% YesAritmia AMC YES 47 targeted A >99% Yes

CARDIO panel

Vision dis. AMC No 232 WES C YesVision dis. Nijmegen No 272 WES CHearing impairment

Nijmegen No 119 WES Clens luxatie VUMC ja 5 targeted A ja

SENSORY NEURAL DISEASES “gene panel”

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The quality of a sample can/ should be evaluated at 3 levels:

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Reporting

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Research vs Diagnostics

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