ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.1428+1G>A (rs863223542)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198224 SCV000250089 pathogenic not provided 2014-10-23 criteria provided, single submitter clinical testing c.1428+1 G>A: IVS11+1 G>A in intron 11 of the ENG gene (NM_000118.2) The c.1428+1 G>A mutation has been reported previously in association with HHT (McDondal J et al., 2011; Nishida T et al 2012). This mutation destroys the canonical splice donor site in intron 11 and is predicted to cause abnormal gene splicing. Many other splice site mutations in the ENG gene have been reported in association with HHT. Furthermore, the c.1428+1 G>A mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, c.1428+1 G>A in the ENG gene is interpreted as a disease-causing mutation. This variant was found in HHT-ARRHYTHMIA
Invitae RCV000551278 SCV000629556 pathogenic Hereditary hemorrhagic telangiectasia 2020-10-15 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 11 of the ENG gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Loss-of-function variants in ENG are known to be pathogenic. This particular variant has been reported in multiple unrelated individuals with hemorrhagic telangiectasia (PMID: 21158752, 22991266, Invitae). ClinVar contains an entry for this variant (Variation ID: 213216). For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286561 SCV001473155 pathogenic Hereditary hemorrhagic telangiectasia type 1 2019-08-09 criteria provided, single submitter clinical testing The ENG c.1428+1G>A variant (rs863223542) has been reported in the literature individuals affected with HHT (Nishida 2012, McDonald 2011), as well as identified by our laboratory in several affected individuals. The variant is reported in ClinVar (Variation ID: 213216) and is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant disrupts the canonical splice donor site of intron 11, which is likely to negatively impact gene function. Based on available information, this variant is considered to be pathogenic. REFERENCES Nishida T et al. Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: gene-phenotype correlations. Am J Med Genet A. 2012 Nov;158A(11):2829-34. McDonald J et al. Molecular diagnosis in hereditary hemorrhagic telangiectasia: findings in a series tested simultaneously by sequencing and deletion/duplication analysis. Clin Genet. 2011;79(4):335-344.

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.