Diagnosis

Establish or confirm diagnosis

Individuals with clinical features of congenital dyserythropoietic anemia.

Is research allowed on the sample after clinical testing is complete? Help
Research testing is only performed under IRB approved protocol with an opt-out policy in place.

This next-generation sequencing assay is performed to test for the presence of a mutation in targeted regions of the following 10 genes: C15ORF41, CDAN1, GATA1, HBB, HBD, KIF23, KLF1, RPS19, SEC23B, and UGT1A. See Targeted Genes Interrogated by NGCDA Next-Generation Sequencing in Special Instructions for details regarding the targeted gene … This next-generation sequencing assay is performed to test for the presence of a mutation in targeted regions of the following 10 genes: C15ORF41, CDAN1, GATA1, HBB, HBD, KIF23, KLF1, RPS19, SEC23B, and UGT1A. See Targeted Genes Interrogated by NGCDA Next-Generation Sequencing in Special Instructions for details regarding the targeted gene regions identified by this test. This is a laboratory-developed test using Research Use Only reagents. Next-generation sequencing (NGS) is performed using the Illumina MiSeq instrument with paired-end, 151-base pair (bp) reads. The DNA is prepared for NGS using a custom Agilent SureSelect Target Enrichment System. Data is analyzed with the CLC Genomics Server Program. Supplemental or confirmatory Sanger sequencing is performed when necessary. View more

Positive results are confirmed when appropriate.

Tests performed
Entire test performed in-house

Analytical sensitivity, specificity, and accuracy are ≥ 99%.

Clinical: Some individuals may have a mutation that is not identified by the methods performed. The absence of a mutation, therefore, does not eliminate the possibility of hereditary hemolytic anemia or a related disorder. This assay does not distinguish between germline and somatic alterations, particularly with variant allele frequencies (VAF) … Clinical: Some individuals may have a mutation that is not identified by the methods performed. The absence of a mutation, therefore, does not eliminate the possibility of hereditary hemolytic anemia or a related disorder. This assay does not distinguish between germline and somatic alterations, particularly with variant allele frequencies (VAF) significantly lower than 50%. Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete. If there is a family history of hereditary hemolytic anemia or a related disorder, it is often useful to test first-degree family members to help establish the clinical significance of variants of unknown significance. At this time, it is not standard practice for the laboratory to systematically review likely pathogenic variants or variants of uncertain significance that have been previously detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time. Technical: Some genetic or genomic alterations, such as large insertion/deletion (indel) events, copy number alterations and gene translocation events are not detected by this assay. The depth of coverage may be variable for some target regions, but assay performance below the minimum acceptable criteria or for failed regions will be noted. Additionally, rare polymorphisms may be present that could lead to false-negative or false-positive results. If results do not match clinical findings, consider alternative methods for analyzing these genes, such as Sanger sequencing or large deletion/duplication analysis. If the patient has had an allogenic blood transfusion, these results may be inaccurate due to the presence of donor DNA. View more

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Alternative Assessment

Software used to interpret novel variations Help
Variants may be analyzed using any combination of the following: Alamut, REVEL, Polyphen-2, SIFT, AGVGD, MutationTaster, SpliceSiteFinder-like, MaxEntScan, NNSPLICE, GeneSplicer, gene-specific online databases, ISCA, UCSC Genome Browser

Laboratory's policy on reporting novel variations Help
All novel variants and copy number variants are evaluated for potential pathogenicity and included in the written report, accordingly.