4-54274887-CA-TG
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006206.6(PDGFRA):c.1700_1701delCAinsTG(p.Pro567Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P567P) has been classified as Benign.
Frequency
Consequence
NM_006206.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.1700_1701delCAinsTG | p.Pro567Leu | missense_variant | 1 | NM_006206.6 | ENSP00000257290.5 | |||
ENSG00000282278 | ENST00000507166.5 | c.1018-38_1018-37delCAinsTG | intron_variant | Intron 12 of 23 | 2 | ENSP00000423325.1 | ||||
PDGFRA | ENST00000509092.5 | n.1518_1519delCAinsTG | non_coding_transcript_exon_variant | Exon 11 of 15 | 1 | |||||
PDGFRA | ENST00000509490.5 | n.1700_1701delCAinsTG | non_coding_transcript_exon_variant | Exon 12 of 18 | 1 | ENSP00000424218.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 567 of the PDGFRA protein (p.Pro567Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 459018). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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
The c.1700_1701delCAinsTG variant (also known as p.P567L), located in coding exon 11 of the PDGFRA gene, results from an in-frame deletion of CA and insertion of TG at nucleotide positions 1700 to 1701. This results in the substitution of the proline residue for a leucine residue at codon 567, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
not specified Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at