NGS Types of gene dossier applications UKGTN can evaluate

Transcription

1 NGS Types of gene dossier applications UKGTN can evaluate Jo Whittaker on behalf of the Genetic Test Evaluation Working Group & UKGTN Project team

2 NGS used in a number of ways Replacement technology for targeted gene testing sequence one or a small number of genes that were previously sequenced sequentially by Sanger sequencing to identify mutations for a specific disorder Targeted or virtual panel tests (from 2 to >100 genes) interrogate a set of genes associated with a particular phenotype or group of phenotypes to identify variations or mutations that can lead to a genetic disorder Exome sequencing studying all the genes known to cause genetically inherited diseases (clinical exome) or the whole coding region of the genome (whole exome) to identify variations or mutations that could cause a genetic disorder Whole genome sequencing

3 1. Laboratories submitting gene dossiers or additional provider forms have validated their test pipelines (targeting, sequencing and bioinformatics analysis) and verified their individual panel tests to meet the guidelines specified by the ACGS ( this will be assessed from the responses to questions 9, 10, 11 (pipeline validation data) and 20 (panel or sub-panel test verification) data for the pipeline validation and panel/sub-panel verification should include a summary of the results for the numbers of unique variants in different categories ( eg SNVs, indels with size range detected) for which the lab has investigated the concordance of its results for NGS and another gold standard method.

4 2. Laboratories submitting gene dossiers or additional provider forms have appropriate expertise to report the test results. this will be assessed from the responses to questions 12 (Are you providing this test already) and 13 ( Is there specialised clinical /research expertise available to the lab?) this is also evidenced through the issue of clinical reports using the new NGS test before the gene dossier is submitted

5 3. A defined panel of genes appropriate to a phenotype/clinical presentation can be described. There is no upper limit on the number of genes than can be interrogated provided that:- the dossier clearly lists which genes are being tested for which disorder/phenotype in a panel or sub-panel there is sufficient evidence that a mutation in one of the genes listed can cause the given phenotype/disease; all genes where the primary phenotype associated with a gene may not be the phenotype under test are identified and systems are in place to handle reporting of these results (questions 28, 29 and 30) test referral criteria are defined The GTEWG may refer the list of phenotypes/genes to be tested to an external expert/group of experts for ratification.

6 4. Gene dossiers submitted for exome sequencing of patients with a specific phenotype, which do not fulfil any diagnostic criteria or for whom routine diagnostic testing has not provided a diagnosis if:- referral criteria for the test population can be defined the rationale for the exome sequencing approach can be described, including the level of evidence required to report a variant as disease causing. This should be included as a separate section in question 9 of the dossier a strategy is included for handling incidental findings (questions 29, 29 and 30)

7 4. Gene dossiers submitted for exome sequencing (contd) where the pipeline is effectively the test, data for that pipeline validation must be given in sufficient detail for another laboratory to repeat the test; in addition to the information required for panel tests the parameters used to filter the data to identify clinically significant variants must be described in question 11 of the gene dossier

8 Looking forward to hearing your expert opinion on today s topics