rs545359247
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_006206.6(PDGFRA):c.809A>C(p.Lys270Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. K270R) has been classified as Uncertain significance.
Frequency
Consequence
NM_006206.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.809A>C | p.Lys270Thr | missense_variant | 6/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.809A>C | p.Lys270Thr | missense_variant | 6/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000509092.5 | n.627A>C | non_coding_transcript_exon_variant | 5/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.809A>C | p.Lys270Thr | missense_variant, NMD_transcript_variant | 6/18 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251332Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135828
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461860Hom.: 0 Cov.: 33 AF XY: 0.0000206 AC XY: 15AN XY: 727242
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74452
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 270 of the PDGFRA protein (p.Lys270Thr). This variant is present in population databases (rs545359247, gnomAD 0.02%). 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: 571306). 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 | Oct 15, 2019 | The p.K270T variant (also known as c.809A>C), located in coding exon 5 of the PDGFRA gene, results from an A to C substitution at nucleotide position 809. The lysine at codon 270 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly 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