rs147733970
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_006206.6(PDGFRA):c.1567T>A(p.Ser523Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,116 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S523S) has been classified as Likely benign.
Frequency
Consequence
NM_006206.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.1567T>A | p.Ser523Thr | missense_variant | 11/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.1567T>A | p.Ser523Thr | missense_variant | 11/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000509092.5 | n.1385T>A | non_coding_transcript_exon_variant | 10/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.1567T>A | p.Ser523Thr | missense_variant, NMD_transcript_variant | 11/18 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251106Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135720
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1460922Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726870
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74372
ClinVar
Submissions by phenotype
Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 29, 2023 | - - |
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 523 of the PDGFRA protein (p.Ser523Thr). This variant is present in population databases (rs147733970, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PDGFRA-related conditions. ClinVar contains an entry for this variant (Variation ID: 459010). 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) performed at Invitae indicates that this missense variant is not expected to disrupt PDGFRA protein function with a negative predictive value of 80%. 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