4-54272441-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_006206.6(PDGFRA):c.1285G>A(p.Gly429Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000436 in 1,613,848 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G429E) 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 -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRA | NM_006206.6 | c.1285G>A | p.Gly429Arg | missense_variant | 9/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.1285G>A | p.Gly429Arg | missense_variant | 9/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000509092.5 | n.1103G>A | non_coding_transcript_exon_variant | 8/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.1285G>A | p.Gly429Arg | missense_variant, NMD_transcript_variant | 9/18 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000335 AC: 51AN: 152068Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000370 AC: 93AN: 251306Hom.: 0 AF XY: 0.000405 AC XY: 55AN XY: 135810
GnomAD4 exome AF: 0.000447 AC: 653AN: 1461662Hom.: 0 Cov.: 32 AF XY: 0.000432 AC XY: 314AN XY: 727152
GnomAD4 genome AF: 0.000335 AC: 51AN: 152186Hom.: 0 Cov.: 31 AF XY: 0.000336 AC XY: 25AN XY: 74400
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 23, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with malignant pleural mesothelioma (Bueno 2016); This variant is associated with the following publications: (PMID: 22703879, 26928227, 20071345) - |
Uncertain significance, no assertion criteria provided | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jul 13, 2012 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 09, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 18, 2018 | The p.G429R variant (also known as c.1285G>A), located in coding exon 8 of the PDGFRA gene, results from a G to A substitution at nucleotide position 1285. The glycine at codon 429 is replaced by arginine, an amino acid with dissimilar properties. This variant has been reported in two individuals with a personal history of total anomalous pulmonary venous return (TAPVR) (Bleyl SB et al. Hum. Mol. Genet., 2010 Apr;19:1286-301), as well as an individual with primary malignant pleural mesothelioma (Bueno R et al. Nat. Genet., 2016 Apr;48:407-16). This variant was also detected as a secondary finding in 1 out of 572 ClinSeq participants, unselected for personal or family history of cancer, who underwent exome sequencing; however, the clinical information for this particular individual was not provided (Johnston JJ et al. Am. J. Hum. Genet., 2012 Jul;91:97-108). This amino acid position is well 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:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Idiopathic hypereosinophilic syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at