NM_002609.4(PDGFRB):c.1998C>A (p.Asn666Lys) AND Infantile myofibromatosis

Clinical significance:Pathogenic (Last evaluated: Feb 1, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000454371.1

Allele description [Variation Report for NM_002609.4(PDGFRB):c.1998C>A (p.Asn666Lys)]

NM_002609.4(PDGFRB):c.1998C>A (p.Asn666Lys)

Gene:
PDGFRB:platelet derived growth factor receptor beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q32
Genomic location:
Preferred name:
NM_002609.4(PDGFRB):c.1998C>A (p.Asn666Lys)
HGVS:
  • NC_000005.10:g.150124275G>T
  • NG_023367.1:g.36585C>A
  • NM_001355016.2:c.1806C>A
  • NM_001355017.2:c.1515C>A
  • NM_002609.4:c.1998C>AMANE SELECT
  • NP_001341945.1:p.Asn602Lys
  • NP_001341946.1:p.Asn505Lys
  • NP_002600.1:p.Asn666Lys
  • NC_000005.9:g.149503838G>T
  • NM_002609.3:c.1998C>A
Protein change:
N505K
Links:
dbSNP: rs864309711
NCBI 1000 Genomes Browser:
rs864309711
Molecular consequence:
  • NM_001355016.2:c.1806C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001355017.2:c.1515C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002609.4:c.1998C>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
protein gain of function [Variation Ontology: 0040]

Condition(s)

Name:
Infantile myofibromatosis (IMF)
Synonyms:
FIBROMATOSIS, CONGENITAL GENERALIZED
Identifiers:
MedGen: C0432284; OMIM: PS228550

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000494643Demoulin lab,University of Louvain - PDGFRB mutations in myofibromatosiscriteria provided, single submitter
Pathogenic
(Feb 1, 2017)
somatic, not applicableresearch

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providednot applicablenot applicablenot providednot providednot providednot providednot providedresearch
not providedsomaticyes2not providednot providednot providednot providedresearch

Citations

PubMed

PDGFRB mutants found in patients with familial infantile myofibromatosis or overgrowth syndrome are oncogenic and sensitive to imatinib.

Arts FA, Chand D, Pecquet C, Velghe AI, Constantinescu S, Hallberg B, Demoulin JB.

Oncogene. 2016 Jun 23;35(25):3239-48. doi: 10.1038/onc.2015.383. Epub 2015 Oct 12.

PubMed [citation]
PMID:
26455322

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 - PDGFRB mutations in myofibromatosis, SCV000494643.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedresearch PubMed (2)
21not providednot providedresearch PubMed (2)
3not providednot providednot providednot providedresearch PubMed (2)
4not providednot providednot providednot providedresearch PubMed (2)

Description

This mutant constitutively activates receptor signaling in a luciferase assay.

The transfection of this mutant transforms NIH3T3 fibroblasts and induces the formation of foci, demonstrating that the mutant is oncogenic.

Description

This mutation was found in two patients with myofibromatosis in our cohort and has been reported by others. It strongly activates PDGFRB signaling in cell culture (gain of function). It was associated with other mutations in the same gene: in one patient, it was associated with c.1696T>C (p.W566R) and in a second case, with c.1681C>T (p.R561C). Another variant, c.1998C>G, leads to the same amino acid change (p.N666K).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1somaticyesnot providednot providednot provided1not providednot providednot provided
2somaticyesnot providednot providednot provided1not providednot providednot provided
3not applicablenot applicablenot providednot providednot providednot providednot providednot providednot provided
4not applicablenot applicablenot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 17, 2020

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