Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001000940 | SCV001158039 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2021-09-16 | criteria provided, single submitter | clinical testing | The ACVRL1 c.72_79delGAAGCCGT; p.Lys25SerfsTer10 variant, to our knowledge, is not described in the medical literature or in gene-specific databases. It is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting 8 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, several downstream truncating variants have been described in individuals with a clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) and are considered pathogenic (Abdalla 2003, Abdalla 2005, Assis 2007, Bayrak-Toydemir 2006, Lesca 2004). Based on available information, the p.Lys25SerfsTer10 variant is considered pathogenic. References: Abdalla S et al. Disease-associated mutations in conserved residues of ALK-1 kinase domain. Eur J Hum Genet. 2003; 11(4):279-87. Abdalla S et al. Novel mutations and polymorphisms in genes causing hereditary hemorrhagic telangiectasia. Hum Mutat. 2005; 25(3):320-1. Assis A et al. Three novel mutations in the activin receptor-like kinase 1 (ALK-1) gene in hereditary hemorrhagic telangiectasia type 2 in Brazilian patients. J Hum Genet. 2007;52(3):237-43. Bayrak-Toydemir P et al. Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations. Am J Med Genet A. 2006 Mar 1;140(5):463-70. Lesca G et al. Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Hum Mutat. 2004; 23(4):289-99. |
| Invitae | RCV001000940 | SCV002235802 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2022-11-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 811218). This variant has not been reported in the literature in individuals affected with ACVRL1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys25Serfs*10) in the ACVRL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACVRL1 are known to be pathogenic (PMID: 15879500). |