ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.316-2A>C (rs33914668)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507767 SCV000601282 pathogenic not provided 2017-06-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001290616 SCV001478718 pathogenic Beta thalassemia major 2021-01-15 criteria provided, single submitter clinical testing Variant summary: HBB c.316-2A>C (also known as IVS II-849A>C in the literature) 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: Four predict the variant abolishes a 3 acceptor site. However, these predictions have yet to be confirmed by functional studies. Blot hybridization analysis of RNA prepared from the erythoid cells of the patient who carried the variant and was diagnosed with HbS-beta0 thalassemia showed only RNA of normal size. The authors postulated that this may be attributed to the rapid degradation of the abnormal RNA or to the complete absence of an abnormally processed RNA (Padanilam et al, 1986). The variant was absent in 251048 control chromosomes (gnomAD). c.316-2A>C has been reported in the literature in at least an individual affected with Beta Thalassemia Major (Chouk_2004, Padanilam_1986). These data indicate that the variant is very likely to be associated with disease. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000016702 SCV000036972 pathogenic beta^0^ Thalassemia 1986-07-01 no assertion criteria provided literature only
GeneReviews RCV000020335 SCV000040711 pathogenic beta Thalassemia 2015-05-14 no assertion criteria provided literature only
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics RCV000020335 SCV001244422 pathogenic beta Thalassemia 2019-11-25 no assertion criteria provided curation

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.