rs754824764
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_006206.6(PDGFRA):c.1475A>C(p.Lys492Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,858 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. K492E) has been classified as Uncertain significance.
Frequency
Consequence
NM_006206.6 missense
Scores
Clinical Significance
Conservation
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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.1475A>C | p.Lys492Thr | missense_variant | 10/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.1475A>C | p.Lys492Thr | missense_variant | 10/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000509092.5 | n.1293A>C | non_coding_transcript_exon_variant | 9/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.1475A>C | p.Lys492Thr | missense_variant, NMD_transcript_variant | 10/18 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152006Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251100Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135708
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461852Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727232
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152006Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74234
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 492 of the PDGFRA protein (p.Lys492Thr). This variant is present in population databases (rs754824764, gnomAD 0.002%). 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: 407416). 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 13, 2023 | The p.K492T variant (also known as c.1475A>C), located in coding exon 9 of the PDGFRA gene, results from an A to C substitution at nucleotide position 1475. The lysine at codon 492 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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