The final phase of Blueprint Genetics’ all-inclusive process is the geneticist’s statement, which is supported by the insight of a specialized clinician. For positive results, the report generally includes valuable insights into potential treatments, while highlighting any risks the disease presents to the patient. The concluding statement is delivered to you through Nucleus, by mail, or by fax, depending on your preferences.

If the results are negative, the statement helps move toward a potential future diagnosis by ruling out one or more possibilities. The geneticist’s statement may also include recommendations for a different, more comprehensive panel when deemed beneficial. In this event, Blueprint Genetics generally does not require a new sample to run the different panel, so it’s easy for you to order a new panel if needed.

While other genetic testing companies might end the process with delivery of the 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 and clinicians. The clinical evaluation team start by assessing the findings. Assisted by our Clinical Interpretation Platform, our team can instantly query millions of genetic and medical sources.

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 classification of genetic variants. A wrong classification can misguide the clinical judgment in patient care including severe consequences in 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. We believe this is critical information for a healthcare professional who makes clinical decisions based on the test result. Blueprint Genetics submits to ClinVar all variants we classify to help other patients and to enhance the development of the field.

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 2015), the industry standard for clinical genetic diagnostics laboratories.

Our schemes have been validated with tens of thousands rare disease patients and evaluated by several medical and clinical geneticists around the world. 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 mutation databases, and appropriate scientific literature. 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 any identified variants are reviewed alongside the relevant medical and genetic literature.

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 bi-directional Sanger sequencing when they do not meet our stringent NGS quality metrics for a true positive call.
 Reported heterozygous and homo/hemizygous copy number variations with a size <10 and <3 target exons are confirmed by orthogonal methods such as dPCR if the specific CNV has been seen and confirmed less than 3 times at Blueprint Genetics.