The Bone Marrow Failure Region of Interest Analysis was designed in collaboration with hematology experts at Boston Children’s Hospital who identified comprehensiveness and rapid turnaround time as critical elements to a Bone Marrow Failure next-generation sequencing test.
This Region of Interest (ROI) study covers 95 genes, therefore providing a highly comprehensive Bone Marrow Failure sequencing assessment. The Bone Marrow Failure Region of Interest Report includes orthogonally-confirmed variants identified by Next Generation Sequencing and the results of the companion deletion/duplication analysis, if ordered.
This study can be ordered for the proband alone by submitting a sample from the affected individual or as a trio with parental samples included in the analysis.
In the case of a non-diagnostic finding, ordering providers have the option to go beyond the Region of Interest test by ordering an expansion to the Claritas Clinical Exome (Test Code N0527). A new sample will not need to be submitted. Interpretation will be provided in a new report that will be available in 12-14 weeks.
- Assesses 95 genes related to Bone Marrow Failure. The gene list is updated based on input from Claritas scientists and partners.
- In addition to coding regions, select non-coding regions (3 total) are sequenced and analyzed. Deep intron variants (19 total) that have been classified as “Pathogenic” or “Likely Pathogenic” are also sequenced and analyzed. Table 1 below provides the list of non-coding regions and deep intron variants.
- Orthogonally-confirmed variants demonstrate high specificity (PPV~99.998%)
- Orthogonal approach using Illumina NextSeq™ with simultaneous confirmation of 95% of variants on the Thermo Fisher (formerly Life Technologies) Ion Proton™; reported variants that are not orthogonally confirmed are confirmed with Sanger sequencing
- Mean coverage of >100x for both the Illumina NextSeq™ and Thermo Fisher Ion Proton™
- Protein coding sequences and 10 bp of adjacent intronic sequences are analyzed. This assay detects SNVs, insertions, and deletions less than 10 bp
- Adding the companion deletion/duplication analysis (Test Code C0974) increases detection rate for copy number variants and larger indels. If not otherwise indicated, genes in this region of interest are partially or fully covered. Genes with no deletion/duplication coverage are indicated by an asterisk (see below).
Increase the Power of the Assay
- Add companion deletion/duplication testing (Test Code C0974)
- If no diagnostic findings are reported in the ROI, providers can order an expanded interpretation of the whole clinical exome (Test Code N0527)
- If a patient has had a bone marrow transplant or recent blood transfusion, please note this on the requisition form and contact Client Services for the most updated specimen submission guidance.
- Providers may order the BMF-ROI standard gene list (see below for the list of genes analyzed) or without BRCA1 and BRCA2.
Additional Service Highlights
- Providers may request a review of variant classification at any time.
- Providers may access the Interpretive Genomics Service at Boston Children’s Hospital, which provides consultation with experts in genes and/or phenotypes. Please contact MedicalDirector@claritasgenomics.com for more information.
- Claritas Genomics will release raw data files or provide access to exome data via NextCODE to authorized health care providers. Review Data Return Program details here.
Deep Intron Variants:
|ANKRD26||5’ UTR region|
|ATR||c. 6897+464 C>G|
|BRCA1||c. 213-15 A>G|
|GATA2||Intron 4 sequence|
ACD, AK2, ANKRD26, ATR, BRCA1, BRCA2, BRIP1, C6orf25*, CEBPA*, CECR1, CSF3R, CTC1, DDX41*, DKC1, DNAJC21*, EFL1/EFTUD1*, ELANE, ERCC4, ETV6, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF*, FANCG, FANCI, FANCL, FANCM, G6PC3, GALE, GATA1, GATA2, GFI1, GFI1B, HAX1, JAGN1*, LIG4*, MAD2L2*, MECOM, MPL, NBN, NHP2, NOP10, PALB2, PARN*, PAX5, PTEN, RAB27A, RAD51*, RAD51C, RMRP*, RPL11, RPL15, RPL19, RPL23, RPL26, RPL27, RPL31, RPL35A, RPL36, RPL5, RPS10, RPS15, RPS19, RPS24, RPS26, RPS27, RPS27A, RPS28, RPS29, RPS7, RTEL1, RUNX1, SAMD9*, SAMD9L*, SBDS, SLX4, SMARCD2, SRP54*, SRP72, TAZ, TCIRG1, TERC*, TERT, THPO, TINF2, TP53, TSR2*, UBE2T*, USB1, VPS13B, VPS45, WAS, WRAP53
*Companion deletion/duplication analysis is not available for this gene