ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.155del (p.Pro52fs) (rs63750128)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756243 SCV000883993 pathogenic not specified 2018-08-07 criteria provided, single submitter clinical testing The HBB c.155delC; p.Pro52fs variant (also known as Codon 51 (-C) or Pro51fs when numbered from the mature protein, rs63750128) has been reported in at least one individual presenting with hematological data consistent with beta zero-thalassemia heterozygosity (Ringelhann 1993). It is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant creates a frameshift by deleting 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: Ringelhann B et al. Molecular characterization of beta-thalassemia in Hungary. Hum Genet. 1993 Oct;92(4):385-7.
Integrated Genetics/Laboratory Corporation of America RCV001193151 SCV001361822 likely pathogenic Hemoglobinopathy 2019-12-12 criteria provided, single submitter clinical testing Variant summary: HBB c.155delC (p.Pro52LeufsX10) 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 251440 control chromosomes (gnomAD). c.155delC has been reported in the literature in one individual who had the characteristics of beta0-thal heterozygote (Ringelhann_1993). The variant, also known as CD 51 (-C), is reported in hemoglobinopathy databases as a causative mutation associated with beta0-thalassemia (HbVar, Ithanet). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV001078413 SCV001244619 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation

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