rs1060499543
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM4PP3PP5
The NM_002609.4(PDGFRB):c.1697_1702del(p.Trp566_Val568delinsLeu) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 31)
Consequence
PDGFRB
NM_002609.4 inframe_deletion
NM_002609.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
PDGFRB (HGNC:8804): (platelet derived growth factor receptor beta) The protein encoded by this gene is a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer (PDGFB or PDGFD) or a heterodimer (PDGFA and PDGFB). This gene is essential for normal development of the cardiovascular system and aids in rearrangement of the actin cytoskeleton. This gene is flanked on chromosome 5 by the genes for granulocyte-macrophage colony-stimulating factor and macrophage-colony stimulating factor receptor; all three genes may be implicated in the 5-q syndrome. A translocation between chromosomes 5 and 12, that fuses this gene to that of the ETV6 gene, results in chronic myeloproliferative disorder with eosinophilia. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_002609.4
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_002609.4.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 5-150125549-ACCTTCC-A is Pathogenic according to our data. Variant chr5-150125549-ACCTTCC-A is described in ClinVar as [Pathogenic]. Clinvar id is 375555.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150125549-ACCTTCC-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRB | NM_002609.4 | c.1697_1702del | p.Trp566_Val568delinsLeu | inframe_deletion | 12/23 | ENST00000261799.9 | |
PDGFRB | NM_001355016.2 | c.1505_1510del | p.Trp502_Val504delinsLeu | inframe_deletion | 11/22 | ||
PDGFRB | NM_001355017.2 | c.1214_1219del | p.Trp405_Val407delinsLeu | inframe_deletion | 12/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRB | ENST00000261799.9 | c.1697_1702del | p.Trp566_Val568delinsLeu | inframe_deletion | 12/23 | 1 | NM_002609.4 | P1 | |
PDGFRB | ENST00000520579.5 | c.*1011_*1016del | 3_prime_UTR_variant, NMD_transcript_variant | 12/23 | 1 | ||||
PDGFRB | ENST00000520229.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Infantile myofibromatosis Pathogenic:1
Pathogenic, no assertion criteria provided | in vitro;research | Demoulin lab, University of Louvain | Dec 01, 2016 | This mutation was found in one patient 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at