ClinVar Miner

Submissions for variant NC_000011.10:g.5225256_5225875delinsTCTACTT

dbSNP: rs1847513733
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001261502 SCV001438799 pathogenic Beta-thalassemia major 2020-03-19 criteria provided, single submitter clinical testing Variant summary: This HBB c.316-149_*342delinsAAGTAGA variant involves the deletion of 619 bp including the last exon (exon 3) of the HBB gene and insertion of 7 nucleotides. The variant was absent in 21694 control chromosomes (gnomAD SVs database). c.316-149_*342delinsAAGTAGA has been reported in the literature in multiple individuals affected with Beta Thalassemia Major (e.g. Orkin_1979, Baysal_1994, Turner_2016). These data indicate that the variant is very likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Ambry Genetics RCV002322173 SCV002610654 pathogenic Inborn genetic diseases 2016-04-29 criteria provided, single submitter clinical testing The c.316-149_*342delinsAAGTAGA pathogenic mutation (also known as del619 and c.1065del619) is located in the HBB gene. The mutation consists of a deletion of 620 nucleotides and a 7 base-pair insertion. This 620 base-pair deletion, which causes beta-zero-thalassemia, was observed in 13.8% of alleles in north Indian patients and homozygous affected individuals usually have presentation before 1 year of age (Sharma N et al. Eur J Haematol. 2010;84(6):531-7). In another study, this mutation was observed in 18.4% (138/750) of beta-thalassemia alleles in Pakistani carriers. However, the consanguinity rate in this population is 55% (Moatter T et al. Int J Hematol. 2012;95(4):394-8). In addition to the clinical data presented in the literature, since gross deletions are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).

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