NM_002609.4(PDGFRB):c.1615_1616insGAT (p.Ile538_Leu539insArg) AND Infantile myofibromatosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 1, 2016
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000454368.1

Allele description [Variation Report for NM_002609.4(PDGFRB):c.1615_1616insGAT (p.Ile538_Leu539insArg)]

NM_002609.4(PDGFRB):c.1615_1616insGAT (p.Ile538_Leu539insArg)

Gene:

PDGFRB:platelet derived growth factor receptor beta [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_002609.4(PDGFRB):c.1615_1616insGAT (p.Ile538_Leu539insArg)

HGVS:

NC_000005.10:g.150126578_150126579insATC
NG_023367.1:g.34281_34282insGAT
NM_001355016.2:c.1423_1424insGAT
NM_001355017.2:c.1132_1133insGAT
NM_002609.4:c.1615_1616insGATMANE SELECT
NP_001341945.1:p.Ile474_Leu475insArg
NP_001341946.1:p.Ile377_Leu378insArg
NP_002600.1:p.Ile538_Leu539insArg
NC_000005.9:g.149506141_149506142insATC
NM_002609.3:c.1615_1616insGAT

Links:

dbSNP: rs1060499541

NCBI 1000 Genomes Browser:

rs1060499541

Molecular consequence:

NM_001355016.2:c.1423_1424insGAT - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001355017.2:c.1132_1133insGAT - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_002609.4:c.1615_1616insGAT - inframe_insertion - [Sequence Ontology: SO:0001821]

Functional consequence:

protein gain of function [Variation Ontology: 0040]

Condition(s)

Name:: Infantile myofibromatosis (IMF)
Synonyms:: Congenital generalized fibromatosis
Identifiers:: MONDO: MONDO:0016824; MedGen: C0432284; OMIM: PS228550

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000484406	Demoulin lab, University of Louvain	no assertion criteria provided	Pathogenic (Dec 1, 2016)	somatic, not applicable	research, in vitro	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000484406

Demoulin lab, University of Louvain

no assertion criteria provided

Pathogenic
(Dec 1, 2016)

somatic, not applicable

research, in vitro

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	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	in vitro
not provided	somatic	yes	2	not provided	not provided	not provided	not provided	research

Citations

PubMed

PDGFRB gain-of-function mutations in sporadic infantile myofibromatosis.

Arts FA, Sciot R, Brichard B, Renard M, de Rocca Serra A, Dachy G, Noël LA, Velghe AI, Galant C, Debiec-Rychter M, Van Damme A, Vikkula M, Helaers R, Limaye N, Poirel HA, Demoulin JB.

Hum Mol Genet. 2017 May 15;26(10):1801-1810. doi: 10.1093/hmg/ddx081.

PubMed [citation]

PMID:: 28334876

Details of each submission

From Demoulin lab, University of Louvain, SCV000484406.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		1	not provided	not provided	research	PubMed (1)
2		1	not provided	not provided	research	PubMed (1)
3	not provided	not provided	not provided	not provided	in vitro	PubMed (1)

Description

This mutant constitutively activates receptor signaling in a luciferase assay.

Description

This mutation was found in two patients with myofibromatosis. It strongly activates PDGFRB signaling in cell culture (gain of function). We sequenced PDGFRB in myofibromatosis cases using the Ion Torrent technology. All variants were confirmed by an alternative method (allele specific PCR or Sanger sequencing). Mutants were functionally characterized in experiments based on cell transfection.

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

Last Updated: May 27, 2023

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