ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.1377+2T>G (rs1555153854)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000640448 SCV000762039 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2017-11-14 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in the last intron (intron 9) of the ACVRL1 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ACVRL1-related disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. A truncation (p.Arg479*) and a subgenic deletion (Ex10del) that lie downstream of this variant has been determined to be pathogenic (PMID: 15024723, 23722869, 16861286, 20414677). This suggests that deletion of this region of the ACVRL1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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