ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.632G>A (p.Gly211Asp) (rs28936687)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001392 SCV001158598 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2019-04-12 criteria provided, single submitter clinical testing The ACVRL1 c.632G>A; p.Gly211Asp variant (rs28936687) is reported in the medical literature in an individual with HHT and pulmonary hypertension (Harrison 2003). ARUP has also detected this variant in an individual with a clinical diagnosis of HHT and family history. Additionally, other variants in this codon, p.Gly211Ser and p.Gly211Cys, have been described in individuals with a diagnosis of HHT or pulmonary hypertension (Heimdal 2016, Yang 2018). The c.632G>A; p.Gly211Asp variant is reported in the ClinVar database (Variation ID: 8253) and is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The amino acid at this position is highly conserved and computational algorithms (PolyPhen-2, SIFT) predict this variant is deleterious. Considering available information, this variant is classified as pathogenic. References: Harrison RE et al. Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia. J Med Genet. 2003 Dec;40(12):865-71. Heimdal K et al. Mutation analysis in Norwegian families with hereditary hemorrhagic telangiectasia: founder mutations in ACVRL1. Clin Genet. 2016 Feb;89(2):182-6. Yang H et al. Genetic analyses in a cohort of 191 pulmonary arterial hypertension patients. Respir Res. 2018 May 9;19(1):87.
NIHR Bioresource Rare Diseases, University of Cambridge RCV001001392 SCV001439467 likely pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2018-01-01 criteria provided, single submitter research PS3+PM2+PP4+PP5
OMIM RCV000008741 SCV000028950 pathogenic Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia 2003-12-01 no assertion criteria provided literature only

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