ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.523+1G>A

dbSNP: rs113930974
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001387969 SCV001588749 pathogenic Hereditary hemorrhagic telangiectasia 2020-05-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ENG are known to be pathogenic (PMID: 15879500). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 23535011, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 4 of the ENG gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Ambry Genetics RCV002341830 SCV002645334 likely pathogenic Cardiovascular phenotype 2019-12-19 criteria provided, single submitter clinical testing The c.523+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 4 of the ENG gene. In our internal cohort, this alteration was identified in an individual with a clinical diagnosis of hereditary hemorrhagic telangiectasia. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.

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.