The Primary Immunodeficiency Region of Interest is designed to facilitate rapid genetic diagnosis of patients with hereditary Primary Immunodeficiency. Such patients may have a disease that would benefit from immediate treatment and customized clinical management.
Developed in collaboration with experts in the Division of Immunology at Boston Childrens Hospital, this Region of Interest evaluates 283 genes related to the known causes of Primary Immunodeficiency within a rapid turnaround time. The Rapid Report, which includes orthogonally-confirmed diagnostic or likely diagnostic findings, is issued within 4 weeks. The Complete Report, issued in an additional 7 weeks includes additional clinically-relevant, confirmed variants and the results of the companion deletion/duplication analysis, if ordered.
Clinical Phenotypes Evaluated
- Innate Immunity with Invasive Bacterial Infections
- Mendelian Susceptibility to Mycobacterial Diseases
- Predisposition to Severe Viral Infections
- EBV Disease
- Combined Immunodeficiency
- B Cell Defects and Antibody Deficiencies
- Autoimmune Lymphoproliferative Disease
- Immune Dysregulatory Disease
- Early-Onset Colitis
- Hemophagocytic Lymphohistiocytosis
- Defects in Major Histocompatibility Complexes
- Assesses 283 genes related to Primary Immunodeficiency. This gene list is updated based on input from Claritas scientists and partners.
- Orthogonally-confirmed variants demonstrate high specificity (PPV~99.998%)
- Orthogonal approach using Illumina NextSeq with simultaneous confirmation of 95% of variants on the ThermoFisher Ion Proton
- Remaining phenotypically-relevant variants are Sanger sequenced so that all reported variants are confirmed
- Mean coverage of >100x for both the Illumina NextSeq and LIFE Ion Proton
- Exons +/- 10bp, relevant 5UTR, 3UTR, and promoter/regulatory regions are evaluated.
- This assay detects SNVs, insertions, and deletions less than 10 bp
- Adding the companion deletion/duplication analysis (test code C0892) increases detection rate for copy number variants and larger indels.
- If a patient has had a bone marrow transplant, please note this on the requisition form and contact Client Services for the most updated specimen submission guidance.
- This entry is for the Trio which includes testing of the Proband and biological parents. See Test Code N0707 for the Proband Only Order.
- The ROI includes analysis of the ACMG56 genes (a list of 56 genes recommended by the American College of Genetics and Genomics, variants in which can lead to health issues and have evidence-based management and/or treatment plans) only to the extent that they are in the gene lists being ordered. However, if a provider orders the Expansion into the Claritas Clinical Exome after the initial analysis, the ACMG56 genes will be examined. Providers who request the Expansion into the Claritas Clinical Exome should discuss the ACMG56 with the patient. More information about the ACMG56 is available in the Claritas Clinical Exome Informed Consent Guide. It is Claritas policy to report on the ACMG56 in the patient unless the patient opts out. Only those findings that are identified in the patient will be evaluated in the parental samples. The proband and the parent(s) may choose to opt-out of having the ACMG56 evaluated. See the Secondary Findings signature page on the requisition form for more details. Note that if the proband opts out, the parent samples will not be evaluated for the ACMG56.
Additional Service Highlights
- Providers may request a review of variant classification at any time.
- Providers may access the Interpretative Genomics Service at Boston Childrens Hospital, which provides consultation with experts in genes and/or phenotypes. Please contact [email protected] for more information.
- Claritas Genomics will release raw data file or provide access to exome data via NextCODE to authorized health care providers. Review Data Return Program details here.