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

dbSNP: rs35099082

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003327489	SCV004034947	pathogenic	not provided	2023-03-14	criteria provided, single submitter	clinical testing	Published functional studies demonstrate partially abnormal spliced RNA which resulted in a frameshift variant, and multiple downstream variants have been reported as pathogenic (Liao et al., 2022, HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 8144358, 36054783, 30275481, 28674233, 10335984, 35615327, 27829298)
Invitae	RCV003327489	SCV004294097	pathogenic	not provided	2023-11-28	criteria provided, single submitter	clinical testing	This sequence change falls in intron 2 of the HBB gene. It does not directly change the encoded amino acid sequence of the HBB protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with beta thalassemia (PMID: 8144358, 10335984). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as IVS-II-5 (G‚ÜíC). ClinVar contains an entry for this variant (Variation ID: 869356). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing resulting in multiple RNA products (PMID: 10335984). For these reasons, this variant has been classified as Pathogenic.
The ITHANET community portal, The Cyprus Institute of Neurology and Genetics	RCV001078427	SCV001244642	pathogenic	beta Thalassemia	2019-11-25	no assertion criteria provided	curation