PMC Bone Marrow Failure Syndromes Panel

Associated Conditions
- 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia (MEGCANN)
- Acute myeloid leukemia, familial
- Amegakaryocytic thrombocytopenia
- Anemia, dyserythropoietic congenital
- Anemia, sideroblastic 2, pyridoxine-refractory
- Anemia, sideroblastic, Protoporphyria, erythropoietic
- Anemia, without thrombocytopenia, Thrombocytopenia with beta-thalessemia,, Dyserythropoietic anemia with thrombocytopenia
- Aplastic anemia, Myelodysplastic syndrome, Acute myelogenous leukemia, Bone marrow failure
- Aplastic anemia, Pulmonary fibrosis and/or bone marrow failure, telomere-related
- Ataxia-pancytopenia syndrome
- Ataxia-Telangiectasia
- Autoimmune lymphoproliferative syndrome, type IB
- Autoinflammatory-pancytopenia syndrome
- Baller-Gerold syndrome, RAPADILINO syndrome, Rothmund-Thomson syndrome
- Baraitser-Winter syndrome
- Bloom syndrome
- Bone marrow failure syndrome 1
- Bone marrow failure syndrome 2
- Bone marrow failure syndrome 3
- Cardiofaciocutaneous syndrome
- Cerebroretinal microangiopathy with calcifications and cysts
- Chediak-Higashi syndrome
- Coats Plus syndrome
- Cohen syndrome
- Colorectal cancer, Li-Fraumeni syndrome, Ependymoma, intracranial, Choroid plexus papilloma, Adrenocortical carcinoma, Osteogenic sarcoma, Hepatoblastoma, Non-Hodgkin lymphoma
- Congenital dyserythropoietic anemia
- Costello syndrome, Congenital myopathy with excess of muscle spindles
- Cutaneous telangiectasia and cancer syndrome, Seckel syndrome
- Deficiency of ADA2
- Dehydrated hereditary stomatocytosis 2
- Diamond-Blackfan anemia
- Diamond-Blackfan anemia 11
- Diamond-Blackfan anemia 15 with mandibulofacial dysostosis
- Diamond-Blackfan anemia 16
- Diarrhea 5, with tufting enteropathy, congenital
- Dursun syndrome
- Dyskeratosis congenita
- Dyskeratosis congenita, autosomal dominant 6
- Dyskeratosis congenita, autosomal recessive 7
- Familial myeloproliferative/lymphoproliferative neoplasms, multiple types, susceptibility to
- Fanconi anemia (FA)
- Fanconi anemia, Xeroderma pigmentosum, XFE progeroid syndrome
- Ghosal hematodiaphyseal syndrome
- Glanzmann thrombasthenia
- Glioma susceptibility 9, Melanoma, cutaneous malignant, susceptibility to 10
- Glycogen storage disease
- Griscelli syndrome
- Griscelli syndrome, Elejalde syndrome
- Hemophagocytic lymphohistiocytosis, familial
- Hereditary breast cancer
- Hermansky-Pudlak syndrome
- Hoyeraal-Hreidarsson syndrome
- Immunodeficiency 23
- Immunodeficiency due to defect in MAPBP-interacting protein
- Immunodeficiency, common variable, 13
- Immunodeficiency, with magnesium defect, Epstein-Barr virus infection and neoplasia, Mental retardation, X-linked 95
- Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovascular malformations
- Isolated or Syndromic neutropenia
- LEOPARD syndrome, Cardiofaciocutaneous syndrome
- Lymphoma, non-Hodgkin, Aplastic anemia, adult-onset, Hemophagocytic lymphohistiocytosis
- Lymphoproliferative syndrome
- Macrothrombocytopenia
- Medulloblastoma, Glioma susceptibility, Pancreatic cancer, Wilms tumor
- Melanoma, familial, Melanoma-pancreatic cancer syndrome
- Metachondromatosis
- Mirage syndrome, Tumoral calcinosis, normophosphatemic
- Muir-Torre syndrome, Endometrial cancer, Colorectal cancer, hereditary nonpolyposis,, Mismatch repair cancer syndrome
- Muir-Torre syndrome, Endometrial cancer, Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposis
- Myelodysplastic syndrome, Chronic neutropenia associated with monocytopenia, evolving to myelodysplasia and acute myeloid leukemia, Acute myeloid leukemia, Emberger syndrome, Immunodeficiency
- Neutropenia
- Neutropenia, severe congenital
- Neutropenia, severe congenital, 2 autosomal dominant, Neutropenia, nonimmune chronic idiopathic, of adults
- Neutropenia, severe congenital, 5, autosomal recessive
- Neutrophil immunodeficiency syndrome
- Neutrophilia, hereditary
- Nijmegen breakage syndrome
- Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia
- Pancreatic cancer, Breast-ovarian cancer, familial
- Periodontitis, juvenile, Haim-Munk syndrome, Papillon-Lefevre syndrome
- Platelet disorder, familial, with associated myeloid malignancy
- Poikiloderma with neutropenia
- POT1 tumor predisposition
- Pre-B cell acute lymphoblastic leukemia
- Primary immunodeficiency
- Pseudo-von Willebrand disease, Bernard-Soulier syndrome
- Pulmonary fibrosis
- Radioulnar synostosis with amegakaryocytic thrombocytopenia 2
- Reticular dysgenesis
- Revesz syndrome
- Sebastian syndrome, May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, Macrothrombocytopenia and progressive sensorineural deafness, Deafness, autosomal dominant 17
- Severe spondylometaphyseal dysplasia
- Shwachman-Diamond syndrome
- Spasticity, childhood-onset, with hyperglycinemia
- Specific granule defiency 2
- Surfactant metabolism dysfunction, pulmonary
- Thiamine-responsive megaloblastic anemia syndrome
- Thrombocythemia 1
- Thrombocytopenia
- Thrombocytopenia - absent radius
- Thrombocytopenia 5
- Thrombocytopenia, Wiskott-Aldrich syndrome
- Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome
- Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndrome
- Wiskott-Aldrich syndrome 2

Methodology

Targeted Exome/ Slice Exome (Next Generation Sequencing including Copy Number Variation)

Coverage

120x

Assay Information
- ATR: Deletion/duplication analysis is not offered for exon 34. Sequencing analysis for exons 34 includes only cds +/- 10 bp.
- BRCA1: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
- RPL19: Sequencing analysis for exons 6 includes only cds +/- 10 bp.
- FANCL: Sequencing analysis for exons 4| 10 includes only cds +/- 10 bp.
- FANCD2: Deletion/duplication analysis is not offered for exons 14-17| 22 and sequencing analysis is not offered for exons 15-17. Sequencing analysis for exons 6| 14| 18| 20| 23| 25| 34 includes only cds +/- 10 bp.
- GFI1: Sequencing analysis for exons 6 includes only cds +/- 0 bp.
- AK2: Deletion/duplication and sequencing analysis is not offered for exon 6.
- RECQL4: Sequencing analysis for exons 13-15 includes only cds +/- 10 bp.
- RBM8A: Analysis includes the non-coding variants NM_005105.4:c.-21G >A and c.67+32G >C.
- EFL1: Deletion/duplication and sequencing analysis is not offered for exons 7| 15.
- BRCA2: Sequence analysis includes +/- 20 base pairs of adjacent intronic sequence.
- TP53: Deletion/duplication analysis covers the promoter region.

Ordering information

Turnaround Time: 10 business days

Preferred Speciment: Saliva Kits (available upon request)

Alternate Specimens: Nail clippings or 3-mL whole blood in purple top EDTA tube

Request a specimen collection kit

Limitations

All sequencing technologies have limitations. A negative result from this analysis does not rule out a possible genetic diagnosis as some variants may not be detected by this test. This test is not designed to detect low level mosaicism, structural rearrangements, indels >40bp, deep intronic variants of unknown clinical significance, or large cytogenetic CNVs. Certain inherent qualities of the human genome, for example repetitive regions/homopolymers, GC rich, pseudogenes, and rare polymorphisms, pose significant technical challenges such as sequence misalignment that may potentially impact the accuracy of the results. False negative results may also occur in the setting of allogeneic bone marrow, stem cell transplantation, active or chronic hematologic conditions, recent blood transfusions, suboptimal DNA quality or PCR trace contamination. Other potential sources of error include sample mix-ups and clerical issues.

References
- 1. Richards S et al. Genetics in medicine. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 2015 May;17(5):405-24 (PMID: 25741868)
- 2. GnomAD (gnomAD)
- 3. CSPEC (ClinGen variant classification rules registry) Criteria Specification Registry
- 4. Normal copy number variation in healthy individuals database of genomic variants: http://dgv.tcag.ca/dgv/app/home
- 5. Riggs, E.R., Andersen, E.F., Cherry, A.M. et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med 22, 245–257 (2020). https://doi.org/10.1038/s41436-019-0686-8
- 6. Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014 Jan 1;42(1):D980-5. doi: 10.1093/nar/gkt1113. PubMed PMID: 24234437.
- 7. Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), Copyright® 1966-2012. World Wide Web URL: http://omim.org.
- 8. http://tinyurl.com/ACMGv4 (ACMG/ Clingen draft Interpretation SOP); clingen_variant-curation_sopv1.pdf

Order a Kit:

New Provider:

Contact:

Test Description

Associated Conditions

Methodology

Coverage

Assay Information

Ordering information

Limitations

References

Tagged Genes