Interpretation

Clinical interpretation and clinical report

The final phase of Blueprint Genetics’ all-inclusive process is the clinical statement. After uncovering the technical results, Blueprint Genetics goes a step further by providing expert clinical interpretation services. This is the phase where the information is put into the knowledgeable hands of world-class geneticists. The clinical interpretation team starts by assessing the findings. Assisted by our Clinical Interpretation Platform, our team can instantly query numerous genetic and medical sources.

For positive results, the report generally includes valuable insights about the identified variant(s), gene function, and associated disease(s) while highlighting risks the disease presents to the patient. Clinical statement within the full report is delivered to you through Nucleus, by mail, or by fax, depending on your preferences.

If the results are negative, the clinical statement crafted by our interpretation team can help inform a potential future diagnosis by ruling out one or more possibilities. If additional testing is considered appropriate, Blueprint Genetics often does not require a new sample, making it easy for you to order an additional test run on that same sample if needed.

How we classify genetic variants when interpreting patients results

In genetic diagnostics, variant classification forms the basis for clinical judgment. Despite the international guidelines and principles, there is still significant inter-laboratory variation in the classification of genetic variants. Variant classification with high-quality interpretation can guide clinical decisions in patient care, including determination of risk stratification among family members.

Blueprint Genetics is dedicated to full transparency in diagnostics, and this includes our variant classification strategy. Our clinical statements provide all the evidence behind our variant classification. This supporting data is crucial to a healthcare professional as test results can be used to guide clinical decisions.

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.

Variants are evaluated using evidence from population and gene-/disease-specific databases, in silico prediction tools, our in-house variant database, multiple publicly and commercially available variant databases, and relevant scientific literature. Our in-house database consists of variants identified through manually curated high-quality data from hundreds of thousands of rare disease patients and their family members covering a wide range of medical categories. To this end, we use points to evaluate variants for potential pathogenicity, with evidence from the relevant databases and literature as the foundation for scoring. The patient’s clinical history and identified variants are reviewed alongside the relevant medical and genetic literature.

Confirmations

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.