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Blueprint Genetics Anemia Panel

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Blueprint Genetics Anemia Panel Anemia Panel Test code: HE0401 Is a 88 gene panel that includes assessment of non-coding variants. Is ideal for patients suspected to have hereditary anemia who have had HBA1 and HBA2 variants excluded as the cause of their anemia or patients suspected to have hereditary anemia who are not suspected to have HBA1 or HBA2 variants as the cause of their anemia. The genes on this panel are included in the Comprehensive Hematology Panel. Is not recommended for patients suspected to have anemia due to alpha-thalassemia (HBA1 or HBA2). These genes are highly homologous reducing mutation detection rate due to challenges in variant call and difficult to detect mutation profile (deletions and gene-fusions within the homologous genes tandem in the human genome). Is not recommended for patients with a suspicion of severe Hemophilia A if the common inversions are not excluded by previous testing. An intron 22 inversion of the F8 gene is identified in 43%-45% individuals with severe hemophilia A and intron 1 inversion in 2%-5% (GeneReviews NBK1404; PMID:8275087, 8490618, 29296726, 27292088, 22282501, 11756167). This test does not detect reliably these inversions. About Anemia Anemia is defined as a decrease in the amount of red blood cells or hemoglobin in the blood. The symptoms of anemia include fatigue, weakness, pale skin, and shortness of breath. Other more serious symptoms may occur depending on the underlying cause. The causes of anemia may be classified as impaired red blood cell (RBC) production or increased RBC destruction (hemolytic anemias). Hereditary anemia may be clinically highly variable, including mild, moderate, or severe forms. Hb Bart syndrome is a severe form of anemia secondary to alpha thalassemia. It is characterized by hydrops fetalis leading to death almost always in utero or shortly after birth. The thalassemias, sickle cell disease, and other hemoglobinopathies represent a major group of inherited disorders of hemoglobin synthesis (HBA1, HBA2, HBB). The thalassemias are among the most common genetic disorders worldwide, occurring more frequently in the Mediterranean region, the Indian subcontinent, Southeast Asia, and West Africa. Hereditary spherocytosis and hereditary elliptocytosis are examples of inherited hemolytic anemias. Hereditary spherocytosis is the most common congenital hemolytic anemia among Caucasians with an estimated prevalence ranging from 1:2,000 to 1:5,000. Availability 4 weeks Gene Set Description Genes in the Anemia Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ABCB7 Anemia, sideroblastic, and spinocerebellar ataxia XL 8 9 ADAMTS13 Schulman-Upshaw syndrome, Thrombotic thrombocytopenic purpura, AR 30 183 familial AK1 Adenylate kinase deficiency, hemolytic anemia due to AR 8 10 ALAS2 Anemia, sideroblastic, Protoporphyria, erythropoietic XL 27 103 AMN Megaloblastic anemia-1, Norwegian AR 29 34 ANK1 Spherocytosis AD/AR 20 105 https://blueprintgenetics.com/ ATM Breast cancer, Ataxia-Telangiectasia AD/AR 1047 1109 ATR Cutaneous telangiectasia and cancer syndrome, Seckel syndrome AD/AR 10 33 ATRX Carpenter-Waziri syndrome, Alpha-thalassemia/mental retardation XL 65 165 syndrome, Holmes-Gang syndrome, Juberg-Marsidi syndrome, Smith- Fineman-Myers syndrome, Mental retardation-hypotonic facies syndrome BLM Bloom syndrome AR 152 119 BRCA2 Fanconi anemia, Medulloblastoma, Glioma susceptibility, Pancreatic AD/AR 3369 2659 cancer, Wilms tumor, Breast-ovarian cancer, familial BRIP1 Fanconi anemia, Breast cancer AD/AR 238 189 C15ORF41 Congenital dyserythropoietic anemia AR 3 3 CDAN1 Anemia, dyserythropoietic congenital AR 12 61 CLCN7 Osteopetrosis AD/AR 15 98 CUBN* Megaloblastic anemia-1, Finnish AR 42 53 CYB5R3 Methemoglobinemia due to methemoglobin reductase deficiency AR 21 71 DHFR* Megaloblastic anemia due to dihydrofolate reductase deficiency AR 2 5 DNAJC21 Bone marrow failure syndrome 3 AR 5 11 DNASE2 Primary immunodeficiency 2 EFL1 Shwachman-Diamond syndrome 3 2 EPB42 Spherocytosis AR 8 17 ERCC4 Fanconi anemia, Xeroderma pigmentosum, XFE progeroid syndrome AR 13 70 FANCA Fanconi anemia AR 191 677 FANCB Fanconi anemia XL 11 21 FANCC Fanconi anemia AR 94 64 FANCD2* Fanconi anemia AR 21 61 FANCE Fanconi anemia AR 4 17 FANCF Fanconia anemia AR 7 16 FANCG Fanconi anemia AR 16 92 FANCI Fanconi anemia AR 13 45 FANCL Fanconi anemia AR 13 24 FANCM Fanconi anemia AR 6 50 G6PD Glucose-6-phosphate dehydrogenase deficiency XL 45 226 https://blueprintgenetics.com/ GATA1 Anemia, without thrombocytopenia, Thrombocytopenia with beta- XL 21 15 thalessemia,, Dyserythropoietic anemia with thrombocytopenia GCLC Gamma-glutamylcysteine synthetase deficiency AR 2 7 GPI Hemolytic anemia, nonspherocytic due to glucose phosphate AR 11 41 isomerase deficiency GSS Glutathione synthetase deficiency AR 8 38 HBA1* Alpha-thalassemia (Hemoglobin Bart syndrome), Alpha-thalassemia AR/Digenic 27 214 (Hemoglobin H disease) HBA2*,# Alpha-thalassemia (Hemoglobin Bart syndrome), Alpha-thalassemia AR/Digenic 44 290 (Hemoglobin H disease) HBB Sickle cell disease, Thalassemia-beta, dominant inclusion body, Other AD/AR/Digenic 242 865 Thalassemias/Hemoglobinopathies, Beta-thalassemia, Hereditary persistence of fetal hemogoblin HFE Hemochromatosis AR/Digenic 11 56 KIF23 Anemia, dyserythropoietic congenital AD 1 3 KLF1 Anemia, dyserythropoietic congenital, Blood group, Lutheran AD/BG 16 45 inhibitor, Hereditary persistence of fetal hemoglobin LPIN2 Majeed syndrome AR 12 14 MTR Methylmalonic acidemia AR 13 43 NBN Breast cancer, Nijmegen breakage syndrome AD/AR 188 97 NT5C3A Uridine 5-prime monophosphate hydrolase deficiency, hemolytic AR 10 28 anemia due to PALB2 Fanconi anemia, Pancreatic cancer, Breast cancer AD/AR 495 406 PC Pyruvate carboxylase deficiency AR 32 41 PDHA1 Leigh syndrome, Pyruvate dehydrogenase E1-alpha deficiency XL 66 192 PDHX Pyruvate dehydrogenase E3-binding protein deficiency AR 14 22 PIEZO1 Dehydrated hereditary stomatocytosis, Lympehedema, hereditary III AD/AR 23 60 PKLR Pyruvate kinase deficiency, Elevation of red blood cell ATP levels, AD/AR 17 277 familial PUS1 Mitochondrial myopathy and sideroblastic anemia AR 7 9 RAD51C Fanconi anemia, Breast-ovarian cancer, familial AD/AR 107 125 REN Hyperuricemic nephropathy, Hyperproreninemia, familial, Renal AD/AR 9 18 tubular dysgenesis RHAG Overhydrated hereditary stomatocytosis, Anemia, hemolytic, Rh-null, AD/AR/BG 13 28 regulator type, Anemia, hemolytic,Rh-Mod type, RHAG blood group RPL11 Diamond-Blackfan anemia AD 12 45 https://blueprintgenetics.com/ RPL15* Diamond-Blackfan anemia AD 2 2 RPL27 Diamond-Blackfan anemia 16 1 1 RPL31 Diamond-Blackfan anemia AD 2 RPL35A Diamond-Blackfan anemia AD 7 14 RPL5 Diamond-Blackfan anemia AD 19 77 RPS10 Diamond-Blackfan anemia AD 3 5 RPS19 Diamond-Blackfan anemia AD 23 172 RPS24 Diamond-Blackfan anemia AD 6 10 RPS26 Diamond-Blackfan anemia AD 10 33 RPS28 Diamond-Blackfan anemia 15 with mandibulofacial dysostosis AD 1 1 RPS29 Diamond-Blackfan anemia AD 4 4 RPS7 Diamond-Blackfan anemia AD 2 10 SBDS* Aplastic anemia, Shwachman-Diamond syndrome, Severe AR 19 90 spondylometaphyseal dysplasia SEC23B Anemia, dyserythropoietic congenital AR 18 121 SLC11A2 Anemia, hypochromic microcytic, with iron overload AR 5 10 SLC19A2 Thiamine-responsive megaloblastic anemia syndrome AR 14 51 SLC25A38 Anemia, sideroblastic 2, pyridoxine-refractory AR 7 27 SLC4A1 Spherocytosis, Ovalcytosis, Renal tubular acidosis, distal, with AD/AR/BG 38 122 hemolytic anemia, Cryohydrocytosis, Acanthocytosis, Band 3 Memphis SLX4 Fanconi anemia AR 18 72 SPTA1 Spherocytosis, Ellipsocytosis, Pyropoikilocytosis AD/AR 29 51 SPTB Spherocytosis, Anemia, neonatal hemolytic, Ellipsocytosis AD/AR 24 99 SRP54 Shwachman-Diamond syndrome AD 3 TCN2 Transcobalamin II deficiency AR 9 35 TF Atransferrinemia AR 8 17 THBD Thrombophilia due to thrombomodulin defect, Hemolytic uremic AD 5 28 syndrome, atypical TMPRSS6 Iron-refractory iron deficiency anemia AR 13 102 TPI1 Triosephosphate isomerase deficiency AR 8 19 XRCC2 Hereditary breast cancer AD/AR 10 21 YARS2 Myopathy, lactic acidosis, and sideroblastic anemia AR 27 11 https://blueprintgenetics.com/ *Some regions of the gene are duplicated in the genome. Read more. # The gene has suboptimal coverage (means <90% of the gene’s target nucleotides are covered at >20x with mapping quality score (MQ>20) reads), and/or the gene has exons listed under Test limitations section that are not included in the panel as they are not sufficiently covered with high quality sequence reads. The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#). Due to possible limitations these genes may not be available as single gene tests. Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), mitochondrial (mi), X-linked (XL), X-linked dominant (XLD) and X-linked recessive (XLR); ClinVar refers to the number of variants in the gene classified as pathogenic or likely pathogenic in this database (ClinVar); HGMD refers to the number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD). The list of associated, gene specific phenotypes are generated from CGD or Mitomap databases. Non-coding disease causing variants covered by the panel Gene Genomic HGVS RefSeq RS-number location HG19 ALAS2 ChrX:55054634 c.-15-2186C>G NM_000032.4 ALAS2 ChrX:55054635 c.-15-2187T>C NM_000032.4 ALAS2 ChrX:55054636 c.-15-2188A>G NM_000032.4 ALAS2 ChrX:55057393
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