ClinVar Miner

Submissions for variant NM_006206.6(PDGFRA):c.2290C>T (p.Arg764Cys)

gnomAD frequency: 0.00001  dbSNP: rs34392012
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000633714 SCV000754987 uncertain significance Gastrointestinal stromal tumor 2023-10-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 764 of the PDGFRA protein (p.Arg764Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PDGFRA-related conditions. ClinVar contains an entry for this variant (Variation ID: 528493). 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. Experimental studies have shown that this missense change does not substantially affect PDGFRA function (PMID: 30389923). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Ambry Genetics RCV001015088 SCV001175882 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-04 criteria provided, single submitter clinical testing The p.R764C variant (also known as c.2290C>T), located in coding exon 15 of the PDGFRA gene, results from a C to T substitution at nucleotide position 2290. The arginine at codon 764 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.