NM_002253.4(KDR):c.1444T>C (p.Cys482Arg) AND Capillary infantile hemangioma

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Jul 7, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000013111.5

Allele description [Variation Report for NM_002253.4(KDR):c.1444T>C (p.Cys482Arg)]

NM_002253.4(KDR):c.1444T>C (p.Cys482Arg)

Gene:

KDR:kinase insert domain receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q12

Genomic location:

Preferred name:

NM_002253.4(KDR):c.1444T>C (p.Cys482Arg)

HGVS:

NC_000004.12:g.55106779A>G
NG_012004.1:g.23817T>C
NM_002253.4:c.1444T>CMANE SELECT
NP_002244.1:p.Cys482Arg
LRG_1198t1:c.1444T>C
LRG_1198:g.23817T>C
LRG_1198p1:p.Cys482Arg
NC_000004.11:g.55972946A>G
NM_002253.2:c.1444T>C
P35968:p.Cys482Arg

Protein change:

C482R; CYS482ARG

Links:

UniProtKB: P35968#VAR_042057; OMIM: 191306.0002; dbSNP: rs34231037

NCBI 1000 Genomes Browser:

rs34231037

Molecular consequence:

NM_002253.4:c.1444T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Capillary infantile hemangioma
Synonyms:: HEMANGIOMA, HEREDITARY CAPILLARY; Hemangioma, capillary infantile, somatic; Hereditary capillary infantile hemangioma
Identifiers:: MONDO: MONDO:0011191; MedGen: C1865871; OMIM: 602089

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000033358	OMIM	no assertion criteria provided	risk factor (Nov 1, 2008)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004015780	KCCC/NGS Laboratory, Kuwait Cancer Control Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jul 7, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033358

OMIM

no assertion criteria provided

risk factor
(Nov 1, 2008)

germline

literature only

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

SCV004015780

KCCC/NGS Laboratory, Kuwait Cancer Control Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jul 7, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma.

Jinnin M, Medici D, Park L, Limaye N, Liu Y, Boscolo E, Bischoff J, Vikkula M, Boye E, Olsen BR.

Nat Med. 2008 Nov;14(11):1236-46. doi: 10.1038/nm.1877. Epub 2008 Oct 19.

PubMed [citation]

PMID:: 18931684
PMCID:: PMC2593632

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]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000033358.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 unrelated patients with infantile hemangioma (602089), Jinnin et al. (2008) identified a germline T-to-C transition in the KDR gene, resulting in a cys482-to-arg (C482R) substitution in the extracellular region. The same change was identified in 8 of 105 additional individuals with hemangioma and in 12 of 295 controls. Expression of FLT1 (165070) in hemangioma endothelial cells was markedly reduced, and KDR activity was increased, compared to controls. In normal endothelial cells, FLT1 transcription is dependent on NFAT (see, e.g., NFATC2; 600490) activation. Further studies indicated that low VEGFR1 expression in hemangioma cells was caused by reduced activity of a pathway involving ITGB1 (135630), TEM8 (ANTXR1; 606410), KDR, and NFAT. The KDR mutation was predicted to result in loss of function and disruption of the normal association of these molecules, leading to an increased risk for development of hemangioma.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From KCCC/NGS Laboratory, Kuwait Cancer Control Center, SCV004015780.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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