rs1057519811
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PM5PP2PP3_Moderate
The NM_006206.6(PDGFRA):c.1729C>A(p.Pro577Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P577S) has been classified as Likely pathogenic.
Frequency
Consequence
NM_006206.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.1729C>A | p.Pro577Thr | missense_variant | 12/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.1729C>A | p.Pro577Thr | missense_variant | 12/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000509092.5 | n.1547C>A | non_coding_transcript_exon_variant | 11/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.1729C>A | p.Pro577Thr | missense_variant, NMD_transcript_variant | 12/18 | 1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 05, 2021 | This sequence change replaces proline with threonine at codon 577 of the PDGFRA protein (p.Pro577Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. 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. Experimental studies have shown that this variant affects PDGFRA protein function (PMID: 30389923). This variant has not been reported in the literature in individuals with PDGFRA-related conditions. This variant is not present in population databases (ExAC no frequency). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 25, 2021 | The p.P577T variant (also known as c.1729C>A), located in coding exon 11 of the PDGFRA gene, results from a C to A substitution at nucleotide position 1729. The proline at codon 577 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.