Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000190599 | SCV000245627 | likely pathogenic | Junctional epidermolysis bullosa with pyloric atresia | 2014-04-23 | criteria provided, single submitter | clinical testing | The c.2783-2A>G variant in ITGB4 has not been reported in individuals with epidermolysis bullosa with pyloric atresia and was absent from large population studies. This variant occurs in the invariant region (+/- 1/2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. In summary, although additional studies are required to fully establish its clinical significance, the c.2783-2A>G variant is likely pathogenic. |
Biomedical Innovation Departament, |
RCV000190599 | SCV001547442 | pathogenic | Junctional epidermolysis bullosa with pyloric atresia | 2018-11-26 | criteria provided, single submitter | research | |
Neuberg Centre For Genomic Medicine, |
RCV000190599 | SCV004101519 | pathogenic | Junctional epidermolysis bullosa with pyloric atresia | criteria provided, single submitter | clinical testing | The splice site variant c.2783-2A>G in ITGB4 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has been reported to the ClinVar database as Likely Pathogenic/Pathogenic. The variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.0003995% is reported in gnomAD. The nucleotide change in ITGB4 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. | |
Invitae | RCV003556234 | SCV004297539 | pathogenic | not provided | 2023-05-22 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individual(s) with epidermolysis bullosa (PMID: 26739954, 34597860). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 208591). This variant is present in population databases (rs758551913, gnomAD 0.003%). This sequence change affects an acceptor splice site in intron 24 of the ITGB4 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ITGB4 are known to be pathogenic (PMID: 11328943, 16473856). |