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 most relevant test results. 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 for variant classification. Information regarding the number of patients with the same variant, their phenotype, available segregation data, citations (publications/mutation databases), and a list of possible additional analysis used such as paralogue annotation can be found in this section of the report. Finally, we also provide information about known pathogenic/likely pathogenic variants in nearby residues if rational.
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, Nucleus.
On the front page, the test result, identified relevant genetic variants, sequencing performance metrics, and a list of the genes in the panel are shown. Variants and their classifications are clearly stated under the subheading test result. Additionally, clinically relevant variants are presented in a variant table with more detailed information. The table displays the gene, variant’s genomic position, variant id, codon, predicted consequence of the change, Genbank accession number for the transcript the mutation nomenclature is based on, mutation nomenclature according to HGVS guidelines, zygosity, minor allele and the minor allele frequency in the gnomAD reference populations (n>120,000), and the classification for the variant. Sequencing performance metrics display the requested panel, full gene list, panel version, target region, and coverage.
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 the in-silico predictions of the variant’s potential pathogenicity when applicable (non-synonymous variants) and the minor allele frequency detected in control cohorts, or number of individuals carrying the same variant, principally in the genome Aggregation Database (gnomAD), comprised of over 120,000 individuals in total.
The review of literature employed in the clinical report outlines the literature and databases assessed in the interpretation process with references. 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 offered. Comprehensive assessment of the literature is essential in the interpretation process and to explain the rationale behind variant classification. Please review our variant classification scheme here. The reporting of variants follows ACMG guidelines, and the mutation nomenclature 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 counselling and family member testing. Test results with benign and likely benign variants are considered negative, and these variants are generally not reported.
Pathogenic and likely pathogenic variants are confirmed by bi-directional Sanger sequencing (sequence variants) or dPCR (CNVs) with an exception of high-quality variants identified more than three times in the laboratory by NGS and CNVs larger than 10 exons. Other variants are confirmed upon judgment. Customers are clearly informed about the variants that were confirmed using orthogonal methods.
Every report is signed by the clinical evaluation team, geneticists, and physicians, who evaluated the sequencing results.
Download a report: Blueprint Genetics Sample Report