4-54288865-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_006206.6(PDGFRA):c.2741G>T(p.Arg914Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006206.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.2741G>T | p.Arg914Leu | missense_variant | Exon 20 of 23 | 1 | NM_006206.6 | ENSP00000257290.5 | ||
ENSG00000282278 | ENST00000507166.5 | c.2021G>T | p.Arg674Leu | missense_variant | Exon 21 of 24 | 2 | ENSP00000423325.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250786Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135488
GnomAD4 exome Cov.: 30
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74298
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:1
This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 914 of the PDGFRA protein (p.Arg914Leu). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with PDGFRA-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PDGFRA protein function. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at