rs368648130
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_006206.6(PDGFRA):c.899A>C(p.Lys300Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000446 in 1,614,214 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. K300E) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.899A>C | p.Lys300Thr | missense_variant | 6/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.899A>C | p.Lys300Thr | missense_variant | 6/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000509092.5 | n.717A>C | non_coding_transcript_exon_variant | 5/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.899A>C | p.Lys300Thr | missense_variant, NMD_transcript_variant | 6/18 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251246Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135798
GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461860Hom.: 0 Cov.: 33 AF XY: 0.0000495 AC XY: 36AN XY: 727236
GnomAD4 genome ? AF: 0.0000459 AC: 7AN: 152354Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74504
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 06, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with a personal and family history of colorectal cancer (Kayser et al., 2018); This variant is associated with the following publications: (PMID: 29987844) - |
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 300 of the PDGFRA protein (p.Lys300Thr). This variant is present in population databases (rs368648130, gnomAD 0.008%). This missense change has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 29978744). ClinVar contains an entry for this variant (Variation ID: 240366). 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 | Feb 19, 2019 | The p.K300T variant (also known as c.899A>C), located in coding exon 5 of the PDGFRA gene, results from an A to C substitution at nucleotide position 899. The lysine at codon 300 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. - |
Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 04-23-2018 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at