Submissions for variant NM_000518.5(HBB):c.30dup (p.Ala11fs)

dbSNP: rs34548294

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001078422	SCV001361821	pathogenic	beta Thalassemia	2022-08-08	criteria provided, single submitter	clinical testing	Variant summary: HBB c.30dupT (p.Ala11CysfsX13) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251216 control chromosomes (gnomAD). c.30dupT has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Beta Thalassemia (e.g. Filon_1995, Ulasli_2015, Unal_2015, Gunes_2021). These data indicate that the variant is very likely to be associated with disease. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Clinical Genetics and Genomics, Karolinska University Hospital	RCV001269760	SCV001450003	pathogenic	not provided	2017-10-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001269760	SCV005877947	pathogenic	not provided	2024-03-26	criteria provided, single submitter	clinical testing	The HBB c.30dup; p.Ala11CysfsTer13 variant (also known as Codons 9/10 (+T) or Ala10fs when numbered from the mature protein, rs34548294, HbVar ID: 787) is reported in the literature in the homozygous or compound heterozygous state in individuals affected with beta (0) thalassemia (Gunes 2021, Ulasli 2015, Unal 2015, see link to HbVar and references therein). This variant is also reported in ClinVar (Variation ID: 869352), but is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. This variant causes a frameshift by inserting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Gunes AK et al. The Spectrum of Beta-Thalassemia Mutations in Syrian Refugees and Turkish Citizens. Cureus. 2021 Jun 4;13(6):e15434. PMID: 34258108. Ulasli M et al. Novel ?eta-Thalassemia Mutation in Turkish Children. Indian J Hematol Blood Transfus. 2015 Jun;31(2):218-22. PMID: 25825561. Unal S et al. The first report of a homozygous codons 9/10 (+T) Beta-thalassemia mutation in a Turkish patient. Hemoglobin. 2015;39(1):66-8. PMID: 25572182.
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics	RCV001078422	SCV001244633	pathogenic	beta Thalassemia	2019-11-25	no assertion criteria provided	curation