Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169544 | SCV000221035 | likely pathogenic | beta Thalassemia | 2015-01-15 | criteria provided, single submitter | literature only | |
Invitae | RCV001850405 | SCV002246990 | pathogenic | not provided | 2021-09-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in insertion of the first 47 nucleotides of intron 2 between exons 2 and 3 or with exon 2 skipping and introduces a new termination codon (PMID: 7151176). However the mRNA is not expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 189128). This variant is also known as IVS-II-1 (G->C). Disruption of this splice site has been observed in individuals with beta thalassemia (PMID: 2446680, 8718703, 27263053, 28391758). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 2 of the HBB gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. |
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RCV000169544 | SCV001244637 | pathogenic | beta Thalassemia | 2019-11-25 | no assertion criteria provided | curation |