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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