ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.20del (p.Glu7fs) (rs63749819)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506769 SCV000603925 pathogenic not provided 2017-05-30 criteria provided, single submitter clinical testing The HBB c.20delA, Glu6fs variant, also known as Codon 6 (-A), has been reported in multiple individuals with beta(0) thalassemia (Bouhass 1990, Gonzalez-Redondo 1988, Kazazian 1983, Rosatelli 1992, HbVar database and references therein). It is listed in the dbSNP variant database (rs63749819), and observed in the Exome Aggregation Consortium general population database at a frequency of 0.0025 percent. The variant introduces a frameshift, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, the variant is classified as pathogenic. REFERENCES Link to HbVar database for Codon 6 (-A): http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=784 Bouhass R et al. A new mutation at IVS1 nt 2(T----A), in beta-thalassemia from Algeria. Blood. 1990; 76(5):1054-5. Kazazian HH Jr et al. beta-Thalassemia due to a deletion of the nucleotide which is substituted in the beta S-globin gene. Am J Hum Genet. 1983; 35(5):1028-33. Gonzalez-Redondo J et al. Clinical and genetic heterogeneity in black patients with homozygous beta-thalassemia from the southeastern United States. Blood. 1988; 72(3):1007-14. Rosatelli M et al. Molecular characterization of beta-thalassemia in the Sardinian population. Am J Hum Genet. 1992; 50(2):422-6.
Counsyl RCV000576555 SCV000677937 pathogenic beta Thalassemia 2015-11-24 criteria provided, single submitter clinical testing p.E7Gfs*13 is classified as a beta-zero mutation.
Integrated Genetics/Laboratory Corporation of America RCV000576555 SCV000697093 pathogenic beta Thalassemia 2016-07-20 criteria provided, single submitter clinical testing Variant summary: The HBB c.20delA (p.Glu7Glyfs) variant results in a premature termination codon, predicted to cause a truncated or absent HBB protein due to nonsense mediated decay (NMD), which are commonly known mechanisms for disease. In addition, this region is known to be a mutational hot-spot. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.27dupG, c.36delT, c.46delT, etc.). This variant was found in 3/121348 control chromosomes at a frequency of 0.0000247, which is lower than the estimated maximal expected allele frequency of a pathogenic HBB variant (0.0111803). This variant is a known common pathogenic variant mainly reported in Algerian, Moroccan, and Sardinian populations in homozygous and/or heterozygous state. Additionally, multiple reputable databases classified this variant as pathogenic. Taken together, this variant is classified as a Pathogenic.
OMIM RCV000016674 SCV000036944 pathogenic beta^0^ Thalassemia 1993-12-01 no assertion criteria provided literature only

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