rs1553904349
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_006206.6(PDGFRA):c.1576dup(p.Thr526AsnfsTer31) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L525L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
PDGFRA
NM_006206.6 frameshift
NM_006206.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.07
Genes affected
PDGFRA (HGNC:8803): (platelet derived growth factor receptor alpha) This gene encodes 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 or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.1576dup | p.Thr526AsnfsTer31 | frameshift_variant | 11/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.1576dup | p.Thr526AsnfsTer31 | frameshift_variant | 11/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000509092.5 | n.1394dup | non_coding_transcript_exon_variant | 10/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.1576dup | p.Thr526AsnfsTer31 | frameshift_variant, NMD_transcript_variant | 11/18 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2019 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in PDGFRA cause disease. This variant has not been reported in the literature in individuals with PDGFRA-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr526Asnfs*31) in the PDGFRA gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at