ClinVar Miner

Submissions for variant NM_000118.3(ENG):c.155G>A (p.Gly52Asp) (rs1564462765)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756077 SCV000883793 pathogenic not provided 2017-07-09 criteria provided, single submitter clinical testing The ENG c.155G>A; p.Gly52Asp variant has previously been reported in a newborn with a family history of hereditary hemorrhagic telangiectasia (HHT) symptoms (Paquet 2001), and the variant was shown to have reduced expression of fully processed endoglin. In addition, other variants at this codon (Gly52Val, Gly52Arg) have been reported in families with HHT (Gallione 1998, Pece-Barbara 1999, Wehner 2006). The p.Gly52Asp variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database). The glycine at codon 52 is well conserved and computational algorithms (SIFT, PolyPhen2, MutationTaster) predict this variant to be damaging to the protein. Based on the above information, this variant is considered pathogenic. REFERENCES Gallione CJ et al. Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles. Hum Mutat. 1998;11(4):286-94. Paquet ME et al. Analysis of several endoglin mutants reveals no endogenous mature or secreted protein capable of interfering with normal endoglin function. Hum Mol Genet. 2001 Jun 15;10(13):1347-57. Pece-Barbara N et al. Expression analysis of four endoglin missense mutations suggests that haploinsufficiency is the predominant mechanism for hereditary hemorrhagic telangiectasia type 1. Hum Mol Genet. 1999 Nov;8(12):2171-81. Wehner LE et al. Mutation analysis in hereditary haemorrhagic telangiectasia in Germany reveals 11 novel ENG and 12 novel ACVRL1/ALK1 mutations. Clin Genet. 2006 Mar;69(3):239-45.
NIHR Bioresource Rare Diseases, University of Cambridge RCV001262053 SCV001439433 likely pathogenic Hereditary hemorrhagic telangiectasia type 1 2018-01-01 criteria provided, single submitter research PS3+PM2+PM1+PP4+PP5

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