NM_001613.2(ACTA2):c.773G>A (p.Arg258His) AND Moyamoya disease 5

Clinical significance:Pathogenic (Last evaluated: May 1, 2009)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000022435.27

Allele description [Variation Report for NM_001613.2(ACTA2):c.773G>A (p.Arg258His)]

NM_001613.2(ACTA2):c.773G>A (p.Arg258His)

Genes:
ACTA2-AS1:ACTA2 antisense RNA 1 [Gene - HGNC]
ACTA2:actin, alpha 2, smooth muscle, aorta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q23.31
Genomic location:
Preferred name:
NM_001613.2(ACTA2):c.773G>A (p.Arg258His)
HGVS:
  • NC_000010.11:g.88939542C>T
  • NG_011541.1:g.56849G>A
  • NM_001141945.2:c.773G>A
  • NM_001613.2:c.773G>A
  • NP_001135417.1:p.Arg258His
  • NP_001604.1:p.Arg258His
  • LRG_781t1:c.773G>A
  • LRG_781t2:c.773G>A
  • LRG_781:g.56849G>A
  • LRG_781p1:p.Arg258His
  • LRG_781p2:p.Arg258His
  • NC_000010.10:g.90699299C>T
  • NM_001141945.1:c.773G>A
  • p.R258H:CGC>CAC
Protein change:
R258H; ARG258HIS
Links:
OMIM: 102620.0002; dbSNP: 121434527
NCBI 1000 Genomes Browser:
rs121434527
Molecular consequence:
  • NM_001613.2:c.773G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Moyamoya disease 5 (MYMY5)
Identifiers:
MedGen: C3279690; Orphanet: 2573; OMIM: 614042
Age of onset:
All ages
Prevalence:
1-9 / 1 000 000 2573

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000043724OMIMno assertion criteria providedPathogenic
(May 1, 2009)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.

Guo DC, Pannu H, Tran-Fadulu V, Papke CL, Yu RK, Avidan N, Bourgeois S, Estrera AL, Safi HJ, Sparks E, Amor D, Ades L, McConnell V, Willoughby CE, Abuelo D, Willing M, Lewis RA, Kim DH, Scherer S, Tung PP, Ahn C, Buja LM, et al.

Nat Genet. 2007 Dec;39(12):1488-93. Epub 2007 Nov 11. Erratum in: Nat Genet. 2008 Feb;40(2):255.

PubMed [citation]
PMID:
17994018

Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.

Guo DC, Papke CL, Tran-Fadulu V, Regalado ES, Avidan N, Johnson RJ, Kim DH, Pannu H, Willing MC, Sparks E, Pyeritz RE, Singh MN, Dalman RL, Grotta JC, Marian AJ, Boerwinkle EA, Frazier LQ, LeMaire SA, Coselli JS, Estrera AL, Safi HJ, Veeraraghavan S, et al.

Am J Hum Genet. 2009 May;84(5):617-27. doi: 10.1016/j.ajhg.2009.04.007. Epub 2009 Apr 30.

PubMed [citation]
PMID:
19409525
PMCID:
PMC2680995

Details of each submission

From OMIM, SCV000043724.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a family of European descent with hereditary thoracic aortic aneurysm with dissection (AAT6; 611788), Guo et al. (2007) identified an 820G-A transition in exon 7 of the ACTA2 gene, resulting in an arg258-to-his (R258H) substitution. One individual in the family had patent ductus arteriosus.

Guo et al. (2009) analyzed 15 individuals carrying a missense mutation at arg258 and found that, in addition to the already established predisposition to TAAD, mutation at this position was associated with stroke (10 individuals with TAAD, 7 with stroke). In 1 family with the R258H mutation, 3 affected individuals had a phenotype consistent with moyamoya disease-5 (MYMY5; 614042). Two of these 3 patients had strokes at ages 44 and 46 years, respectively, and also had thoracic aortic aneurysm with dissection; the third had isolated moyamoya disease with stroke at age 16 years. The findings indicated that ACTA2 mutations can cause a spectrum of vascular diseases, even within a single family.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 26, 2016