Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000821165 | SCV000961912 | pathogenic | Hereditary hemorrhagic telangiectasia | 2018-08-25 | 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, 20656886, 22385575). Different variants affecting this acceptor dinucleotide (c.992-1G>C and c.992-1G>A) have been observed in affected individuals (PMID: 19270816, 16705692). This suggests that this dinucleotide is important for normal RNA splicing, and that other variants at these positions may also be clinically significant. 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. This variant has been observed in an individual affected with hereditary hemorrhagic telangiectasia (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 7 of the ENG gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
NIHR Bioresource Rare Diseases, |
RCV001263085 | SCV001441167 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 1 | 2018-01-01 | criteria provided, single submitter | research | PVS1+PM2+PP4 |
Gene |
RCV001664441 | SCV001875358 | pathogenic | not provided | 2021-02-12 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Reported in ClinVar as a pathogenic variant (ClinVar Variant ID# 663310; Landrum et al., 2016) |
Mayo Clinic Laboratories, |
RCV001664441 | SCV002103223 | pathogenic | not provided | 2021-06-30 | criteria provided, single submitter | clinical testing | PVS1, PM2, PP4 |