rs141047712
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_006206.6(PDGFRA):c.2291G>A(p.Arg764His) variant causes a missense change. The variant allele was found at a frequency of 0.000105 in 1,613,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R764C) 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.2291G>A | p.Arg764His | missense_variant | 16/23 | ENST00000257290.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRA | ENST00000257290.10 | c.2291G>A | p.Arg764His | missense_variant | 16/23 | 1 | NM_006206.6 | P1 | |
PDGFRA | ENST00000507536.1 | n.717G>A | non_coding_transcript_exon_variant | 4/5 | 1 | ||||
PDGFRA | ENST00000509092.5 | n.2109G>A | non_coding_transcript_exon_variant | 15/15 | 1 | ||||
PDGFRA | ENST00000509490.5 | c.*212G>A | 3_prime_UTR_variant, NMD_transcript_variant | 17/18 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000219 AC: 55AN: 251068Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135688
GnomAD4 exome AF: 0.0000992 AC: 145AN: 1461380Hom.: 0 Cov.: 31 AF XY: 0.0000990 AC XY: 72AN XY: 727030
GnomAD4 genome AF: 0.000164 AC: 25AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 17AN XY: 74484
ClinVar
Submissions by phenotype
not provided Uncertain:2
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 | GeneDx | Apr 30, 2024 | In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in an individual with atherosclerosis (PMID: 22703879); This variant is associated with the following publications: (PMID: 27034009, 31645765, 35982159, 33057194, 22703879) - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 14, 2019 | The p.R764H variant (also known as c.2291G>A), located in coding exon 15 of the PDGFRA gene, results from a G to A substitution at nucleotide position 2291. The arginine at codon 764 is replaced by histidine, an amino acid with highly similar properties. This variant was 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(1):97-108). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by BayesDel in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
PDGFRA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 08, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Gastrointestinal stromal tumor Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at