rs760631068
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_006206.6(PDGFRA):c.466G>A(p.Glu156Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000818 in 1,613,938 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. E156D) has been classified as Uncertain significance.
Frequency
Consequence
NM_006206.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.466G>A | p.Glu156Lys | missense_variant | 4/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.466G>A | p.Glu156Lys | missense_variant | 4/23 | 1 | NM_006206.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152096Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000195 AC: 49AN: 251276Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135788
GnomAD4 exome AF: 0.0000773 AC: 113AN: 1461842Hom.: 1 Cov.: 33 AF XY: 0.0000921 AC XY: 67AN XY: 727230
GnomAD4 genome AF: 0.000125 AC: 19AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74284
ClinVar
Submissions by phenotype
PDGFRA-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 08, 2024 | The PDGFRA c.466G>A variant is predicted to result in the amino acid substitution p.Glu156Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.078% of alleles in individuals of South Asian descent in gnomAD. This variant is interpreted as uncertain or likely benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/407397/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 22, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 18, 2019 | The p.E156K variant (also known as c.466G>A), located in coding exon 3 of the PDGFRA gene, results from a G to A substitution at nucleotide position 466. The glutamic acid at codon 156 is replaced by lysine, an amino acid with similar properties. This amino acid position is poorly 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. - |
Gastrointestinal stromal tumor Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at