NM_004444.5(EPHB4):c.802T>C (p.Cys268Arg) AND Capillary malformation-arteriovenous malformation 2

Clinical significance:Uncertain significance (Last evaluated: Mar 29, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_004444.5(EPHB4):c.802T>C (p.Cys268Arg)]

NM_004444.5(EPHB4):c.802T>C (p.Cys268Arg)

EPHB4:EPH receptor B4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_004444.5(EPHB4):c.802T>C (p.Cys268Arg)
  • NC_000007.14:g.100822277A>G
  • NG_052671.1:g.10245T>C
  • NM_004444.5:c.802T>CMANE SELECT
  • NP_004435.3:p.Cys268Arg
  • NC_000007.13:g.100419899A>G
  • NM_004444.4:c.802T>C
Protein change:
C268R; CYS268ARG
OMIM: 600011.0005; dbSNP: rs201816920
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_004444.5:c.802T>C - missense variant - [Sequence Ontology: SO:0001583]


Capillary malformation-arteriovenous malformation 2 (CMAVM2)
MONDO: MONDO:0020785; MedGen: C4748670; OMIM: 618196

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000853239OMIMno assertion criteria providedPathogenic
(Nov 27, 2018)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000994936SIB Swiss Institute of Bioinformaticscriteria provided, single submitter
Uncertain significance
(Mar 29, 2019)

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
not providedunknownunknownnot providednot providednot providednot providednot providedcuration



Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK Signaling.

Amyere M, Revencu N, Helaers R, Pairet E, Baselga E, Cordisco M, Chung W, Dubois J, Lacour JP, Martorell L, Mazereeuw-Hautier J, Pyeritz RE, Amor DJ, Bisdorff A, Blei F, Bombei H, Dompmartin A, Brooks D, Dupont J, González-Enseñat MA, Frieden I, Gérard M, et al.

Circulation. 2017 Sep 12;136(11):1037-1048. doi: 10.1161/CIRCULATIONAHA.116.026886. Epub 2017 Jul 7.

PubMed [citation]

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

Details of each submission

From OMIM, SCV000853239.2

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


In 2 brothers and their affected father and paternal grandmother (family CM-90) with multiple capillary malformations (CMAVM2; 618196), Amyere et al. (2017) identified heterozygosity for a c.802T-C transition in exon 4 of the EPHB4 gene, resulting in a cys268-to-arg (C268R) substitution. The mutation segregated fully with disease in the family and was not found in the ExAC database. The 4 mutation carriers all exhibited capillary malformations, and 1 also showed a Parkes Weber lesion on the right leg.

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

From SIB Swiss Institute of Bioinformatics, SCV000994936.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)


This variant is interpreted as Uncertain significance for Capillary malformation-arteriovenous malformation 2. The following ACMG Tag(s) were applied: PM2: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3: Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1: Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2021

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