Submissions for variant NM_000518.5(HBB):c.315+2T>G

dbSNP: rs63750283

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000506362	SCV000601272	likely pathogenic	not provided	2017-06-24	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001078426	SCV001338950	likely pathogenic	beta Thalassemia	2020-03-16	criteria provided, single submitter	clinical testing	Variant summary: HBB c.315+2T>G 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 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251166 control chromosomes (gnomAD). c.315+2T>G has been reported in the literature in a compound heterozygous patient affected with sickle-cell beta-thalassemia (Rizo-de-la-Torre_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely 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	RCV001078426	SCV001244641	pathogenic	beta Thalassemia	2019-11-25	no assertion criteria provided	curation