ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.625+1G>A

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
Genetics and Molecular Pathology, SA Pathology RCV002466779 SCV002761391 likely pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2019-10-22 criteria provided, single submitter clinical testing This variant is predicted to disrupt normal splicing at the donor site of exon 5 which is likely to be detrimental to the resulting protein. However, confirmation of splicing predictions can only be determined from RNA studies. Therefore, the variant is classified as likely pathogenic.
Ambry Genetics RCV003164724 SCV003864386 likely pathogenic Cardiovascular phenotype 2023-01-03 criteria provided, single submitter clinical testing The c.625+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 4 of the ACVRL1 gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002466779 SCV004409318 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2023-02-18 criteria provided, single submitter clinical testing 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: 1803109). Disruption of this splice site has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 27291782). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 5 of the ACVRL1 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 ACVRL1 are known to be pathogenic (PMID: 15879500).

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.