Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000507915 | SCV000603457 | pathogenic | not specified | 2016-10-07 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001217385 | SCV001389221 | pathogenic | Hereditary hemorrhagic telangiectasia | 2022-11-08 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 439650). This sequence change affects an acceptor splice site in intron 2 of the ENG 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 ENG are known to be pathogenic (PMID: 15879500). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with clinical features of hereditary hemorrhagic telangiectasia (Invitae). It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV004730967 | SCV005337308 | likely pathogenic | ENG-related disorder | 2024-08-08 | no assertion criteria provided | clinical testing | The ENG c.220-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. To our knowledge this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Variants that disrupt the consensus splice acceptor site in ENG are expected to be pathogenic. This variant is interpreted as likely pathogenic. |