The goal of a genomics report is to convey accurate, interpretable and succinct information that is relevant to patient care. In the Massively parallel sequencing era, this simple statement is becoming increasingly difficult to put into practice. This chapter aims to provide guidelines and establish principles that should assist in the preparation of a genomics report.
Approaches to genomic analysis vary in terms of the technology and methodology used as well as the breadth of genetic variation that is interrogated; the analysis may yield information about a single class of genetic variation or may extend to encompass all sequence and structural variants. This presents a number of challenges for the clinical laboratory when preparing a report based on Genomic data. The issue of clinical validity and utility is an important concept to keep in mind when formulating the report, although addressing this is beyond the scope of this document, and is already well covered by existing legislation in NPAAC standard publications (validation of in-house IVDs and nucleic acid testing).
A key issue in reporting genomic tests is that variants of known or possible pathogenicity may be identified which may be unrelated to the primary clinical indication for the test. Such incidental findings are inevitable in high-resolution genomic studies utilising Massively Parallel Sequencing techniques which interrogate a greater proportion of the human genomic sequence, presenting difficulties both for laboratories in reporting such variants and for clinicians receiving unsolicited information. The potential for false positive results is also amplified by the increasing number of genes interrogated, and the low prevalence of some of the disorders which may be the subject of investigation by genomic sequencing.
A second key issue is that a large number of variants of uncertain clinical significance can be identified and the reporting of this information requires careful management to minimise potential harm while providing the maximum available, relevant information, for clinical management.
It is essential that laboratories producing reports of genomic tests have clearly defined, evidence based protocols for classifying the clinical significance of detected genetic variants and addressing incidental findings. This protocol should define, prior to the analytical result being available, which outcomes will be reported and which will not and that these protocols are available to requestors of Genomic tests.
It is also essential that these results are reported clearly, consistently and unambiguously, using established nomenclature guidelines such as those available from the Human Genome Variation Society (http://www.hgvs.org/mutnomen/) and relevant standardised reporting formats such as the RCPA Guidelines for reporting molecular genetic tests to medical practitioners 2009. It must be recognised that laboratory reports may be read by both experts and non-experts, and may be stored for years in a patient’s medical record.
This chapter provides a guide for the reporting of NGS results in the clinical context. It has been developed in the interests of ensuring the analytical and clinical validity of genomic reports, the consistency and clarity of reporting, thereby assisting in the production of a report that is accurate, interpretable, succinct and relevant to patient care.