rs369389595
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_006206.6(PDGFRA):c.3193G>A(p.Glu1065Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,572 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1065D) 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.3193G>A | p.Glu1065Lys | missense_variant | 23/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.3193G>A | p.Glu1065Lys | missense_variant | 23/23 | 1 | NM_006206.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152142Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251262Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135792
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461430Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 727046
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74312
ClinVar
Submissions by phenotype
Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 09, 2023 | - - |
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 14, 2023 | This variant is present in population databases (rs369389595, gnomAD 0.02%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1065 of the PDGFRA protein (p.Glu1065Lys). This variant has not been reported in the literature in individuals affected with PDGFRA-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 573963). - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 23, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at