Clinical statement
The Blueprint Genetics clinical statement provided for customers is a thorough report of the whole diagnostic process and fulfils ISO 15189 quality requirements. Our clinical statement is accessible through our online portal Nucleus, or upon request a printed pdf version of the statement can be sent via mail or fax.
For clarity, the statement is split into sections. The first page of the statement concisely presents the test results with a summary of primary, secondary, and additional findings. Additional pages include basic information of variant’s allele frequencies in reference populations and in silico predictions. The most important part is the careful literature review presenting all the evidence gathered by our team for variant classification. Information regarding the number of other patients with the same variant, their phenotype, available segregation data, citations (publications/variant databases), and a list of possible additional analysis used such as paralogue annotation can be found in this section of the report. We also provide information about known pathogenic/likely pathogenic variants in nearby residues if applicable.
All customers, even those who order results by mail or fax, have access to test results through Nucleus. Some information regarding the applied technologies and detailed sequencing coverage are only available through the electronic report on our online portal.
On the first pages, a summary of all findings, identified relevant genetic variants, sequencing performance metrics, and test information are shown. Variants and their classifications are clearly stated in the summary of results. Additional detailed information is presented in a sequence alterations table which displays the gene name and associated inheritance mode and phenotype, variant’s genomic position, its predicted consequence, Genbank accession number for the transcript, variant nomenclature according to HGVS guidelines, genotype, allele count in the gnomAD reference populations, and the classification of the variant. Sequencing performance metrics with coverage information, test target region with gene list and panel version are also included.
The statement
The patient’s clinical history, provided by the customer, is recapped at the beginning of the statement. This information is extremely valuable for the interpretation process.
The clinical report begins with the most relevant finding. If more than one significant variant is detected, then they are described in order of significance in relation to the clinical history and phenotype of the patient. The first paragraph of the clinical report gives the core information regarding the variant. It covers in silico predictions of the variant’s potential pathogenicity when applicable and the allele frequency detected in control cohorts, or number of individuals carrying the same variant, in the genome Aggregation Database (gnomAD).
The review of literature included in the clinical report outlines the medical literature and databases assessed by our team in the interpretation process. For clarity, the review of literature first focuses specifically on the variant in question. Following the variant-specific literature review, more information on the gene, associated disease(s), and other additional/supporting information is provided. Comprehensive assessment of the literature is essential in the interpretation process and to explain the rationale behind variant classification. Blueprint Genetics has developed a variant classification scheme primarily intended to classify variants in rare monogenic disorders. Our scheme follows the guidelines and interpretation criteria established by the American College of Medical Genetics and Genomics (ACMG), Association for Molecular Pathology (AMP), and ClinGen. Variant nomenclatire is based on HGVS guidelines.
Concluding remarks recap the evidence presented in the clinical report and clarify the rationale for the classification of the identified variant(s). The utility of the genetic test results and possible recommendations for further actions are given. The conclusion also includes recommendations for genetic counseling and family member testing. Test results with benign and likely benign variants are considered negative, and these variants are generally not reported.
The final step in the analysis is orthogonal confirmation. Sequence variants classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS) are confirmed using Sanger sequencing when they do not meet our stringent NGS quality metrics for a true positive call. There can be regional, product, or project-specific confirmation policies agreed on separately in addition to the above mentioned.
Every report is signed by our clinical interpretation experts and laboratory director.
Download a report: Blueprint Genetics Sample Report