rs760631068
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
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).
Frequency
Consequence
NM_006206.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.466G>A | p.Glu156Lys | missense_variant | 4/23 | 1 | NM_006206.6 | ENSP00000257290.5 | ||
ENSG00000282278 | ENST00000507166.5 | c.1018-11160G>A | intron_variant | 2 | ENSP00000423325.1 |
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, no assertion criteria provided | 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 - |
Gastrointestinal stromal tumor Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 17, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 20, 2024 | This alteration is classified as 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