ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.93-22_95del (rs193922563)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000030009 SCV000052664 pathogenic beta Thalassemia 2019-08-28 criteria provided, single submitter clinical testing Variant summary: HBB c.93-22_95del25 is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: five predict the variant abolishes a 3 prime acceptor site, which has been confirmed by a functional study (Orkin_1983). This variant was absent in 251322 control chromosomes (gnomAD). c.93-22_95del25 has been reported in the literature in individuals affected with Beta Thalassemia (Orkin_1983, Adekile_2015). These data indicate that the variant is likely to be associated with disease. No other 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.
Invitae RCV001052793 SCV001217019 pathogenic not provided 2019-12-09 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 1 of the HBB gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with beta-thalassemia (PMID: 6190800, 26076396, 20437613, 23637309). This variant is also known as IVS-1, 25bp del in the literature. ClinVar contains an entry for this variant (Variation ID: 15442). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 6190800). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HBB are known to be pathogenic (PMID: 23637309). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000016700 SCV000036970 pathogenic beta^0^ Thalassemia 1983-07-25 no assertion criteria provided literature only

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