ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.17_18del (p.Pro6fs) (rs34889882)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506399 SCV000601252 pathogenic not provided 2016-11-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586913 SCV000697089 pathogenic beta Thalassemia 2017-06-06 criteria provided, single submitter clinical testing Variant summary: The HBB c.17_18delCT is a frame-shift variant resulting in termination of translation at codon 23, which is predicted to cause either a truncated or absent HBB protein through non-sense mediated decay which is a commonly known mechanism for BTHAL. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Leu29fs). This variant is found in 1/121340 control chromosomes from ExAC at a frequency of 0.0000082, which does not exceed the maximal expected frequency of a pathogenic allele (0.0111803) in this gene. This variant has been commonly identified in beta-thalassemia patients in both compound heterozygous and homozygous states. It is also reported as one of the common mutations in Middle Eastern countries (Lahiry_2008). Taken together, this variant has been classified as a disease variant/pathogenic.
Counsyl RCV000586913 SCV000799824 pathogenic beta Thalassemia 2018-05-08 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002211 SCV001160085 pathogenic not specified 2018-11-05 criteria provided, single submitter clinical testing The HBB c.17_18delCT; p.Pro6fs variant (rs34889882), also known as Codon 5 (-CT) or Pro5fs when numbered from the mature protein, has been reported in the literature in an individual with beta(0) thalassemia (Kollia 1989, HbVar database and references therein). This variant is reported as pathogenic in ClinVar (Variation ID: 15422). It is found in the general population with an overall allele frequency of 0.004% (11/251156 alleles) in the Genome Aggregation Database. This variant causes a frameshift by deleting 2 nucleotides, 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 variant in HbVar database: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=783&.cgifields=histD Kollia et al. Frameshift codon 5 [Fsc-5 (-CT)] thalassemia; a novel mutation detected in a Greek patient. Hemoglobin. 1989;13(6):597-604.
Baylor Genetics RCV001004360 SCV001163298 pathogenic Hb SS disease criteria provided, single submitter clinical testing
Invitae RCV000506399 SCV001215748 pathogenic not provided 2019-12-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro6Argfs*17) in the HBB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs34889882, ExAC 0.006%). This variant has been observed in combination with another HBB variant in an individual affected with beta thalassemia (PMID: 2606727). This variant is also known as Pro5fs and FSC-5(-CT) in the literature. ClinVar contains an entry for this variant (Variation ID: 15422). Loss-of-function variants in HBB are known to be pathogenic (PMID: 23637309). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000016678 SCV000036948 pathogenic beta^0^ Thalassemia 1989-01-01 no assertion criteria provided literature only
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV000586913 SCV001244626 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation

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