Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000508061 | SCV000602418 | pathogenic | not specified | 2016-10-07 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001387731 | SCV001588436 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2020-05-31 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 of the ACVRL1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ACVRL1 are known to be pathogenic (PMID: 15879500). This variant has been reported in several individuals affected with hereditary hemorrhagic telangiectasia (HHT) (PMID: 17384219, 18673552). ClinVar contains an entry for this variant (Variation ID: 439380). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002341193 | SCV002643802 | pathogenic | Cardiovascular phenotype | 2024-11-20 | criteria provided, single submitter | clinical testing | The c.525+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 3 of the ACVRL1 gene. This mutation has been shown to cause a splicing defect. (Gedge F et al. J Mol Diagn. 2007;9(2):258-265). 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. 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. Based on the supporting evidence, this variant is interpreted as a disease-causing mutation. |
| Gene |
RCV004701578 | SCV005201588 | pathogenic | not provided | 2023-11-16 | criteria provided, single submitter | clinical testing | 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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 17384219, 17786384, 18673552, 20067780) |
| Neuberg Centre For Genomic Medicine, |
RCV001387731 | SCV005438773 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2023-07-22 | criteria provided, single submitter | clinical testing | The invariant splice donor variant c.525+1G>A in ACVRL1 gene has been observed in heterozygous state in multiple individuals with hereditary hemorrhagic telangiectasia HHT Fontalba et. al., 2008; Gedge et. al., 2007. The observed variant is absent in gnomAD exomes database. This variant has been submitted to the ClinVar database as Pathogenic multiple submitters. This sequence change affects a donor splice site in intron 4 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 Baralle et. al., 2005, and loss-of-function variants in ACVRL1 are known to be pathogenic Abdalla et. al., 2006. For these reasons, this variant has been classified as Pathogenic. |