rs1553902958
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_006206.6(PDGFRA):c.755A>T(p.Glu252Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 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. E252E) 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.755A>T | p.Glu252Val | missense_variant | 5/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.755A>T | p.Glu252Val | missense_variant | 5/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000508170.5 | c.*1089A>T | 3_prime_UTR_variant | 4/4 | 1 | ||||
PDGFRA | ENST00000509092.5 | n.573A>T | non_coding_transcript_exon_variant | 4/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.755A>T | p.Glu252Val | missense_variant, NMD_transcript_variant | 5/18 | 1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461410Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727024
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 26, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PDGFRA-related disease. ClinVar contains an entry for this variant (Variation ID: 459121). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with valine at codon 252 of the PDGFRA protein (p.Glu252Val). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and valine. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 19, 2024 | The c.755A>T (p.E252V) alteration is located in exon 5 (coding exon 4) of the PDGFRA gene. This alteration results from a A to T substitution at nucleotide position 755, causing the glutamic acid (E) at amino acid position 252 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at