NM_002609.4(PDGFRB):c.1681C>T (p.Arg561Cys) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 21, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000390507.6

Allele description [Variation Report for NM_002609.4(PDGFRB):c.1681C>T (p.Arg561Cys)]

NM_002609.4(PDGFRB):c.1681C>T (p.Arg561Cys)

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.1681C>T (p.Arg561Cys)

Other names:

NM_002609.3(PDGFRB):c.1681C>T(p.Arg561Cys)

HGVS:

NC_000005.10:g.150125571G>A
NG_023367.1:g.35289C>T
NM_001355016.2:c.1489C>T
NM_001355017.2:c.1198C>T
NM_002609.4:c.1681C>TMANE SELECT
NP_001341945.1:p.Arg497Cys
NP_001341946.1:p.Arg400Cys
NP_002600.1:p.Arg561Cys
NC_000005.9:g.149505134G>A
NM_002609.3:c.1681C>T
P09619:p.Arg561Cys

Protein change:

R400C; ARG561CYS

Links:

UniProtKB: P09619#VAR_069925; OMIM: 173410.0003; dbSNP: rs367543286

NCBI 1000 Genomes Browser:

rs367543286

Molecular consequence:

NM_001355016.2:c.1489C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001355017.2:c.1198C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002609.4:c.1681C>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

protein gain of function [Variation Ontology: 0040]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329949	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 21, 2023)	germline	clinical testing	Citation Link,
SCV003824810	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 17, 2022)	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

SCV000329949

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 21, 2023)

germline

clinical testing

Citation Link,

SCV003824810

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 17, 2022)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 GeneDx, SCV000329949.7

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

Description

Published functional studies demonstrate a damaging effect (constitutive activation of the PDGFRB gene and sensitivity to tyrosine kinase inhibitors) (Arts et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23731542, 28286173, 28334876, 23731537, 25158255, 26455322, 28496993, 28183292, 30103666, 31291054, 32500973)

#	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

From Revvity Omics, Revvity, SCV003824810.2

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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