Submissions for variant NM_006206.6(PDGFRA):c.1285G>A (p.Gly429Arg)

gnomAD frequency: 0.00034  dbSNP: rs150577828

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000204962	SCV000261868	likely benign	Gastrointestinal stromal tumor	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000204962	SCV000449736	likely benign	Gastrointestinal stromal tumor	2017-04-27	criteria provided, single submitter	clinical testing	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.
Illumina Laboratory Services, Illumina	RCV000360480	SCV000449737	likely benign	Idiopathic hypereosinophilic syndrome	2017-04-27	criteria provided, single submitter	clinical testing	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.
Ambry Genetics	RCV001010760	SCV001171000	uncertain significance	Hereditary cancer-predisposing syndrome	2018-09-18	criteria provided, single submitter	clinical testing	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.
GeneDx	RCV000034714	SCV001986382	uncertain significance	not provided	2021-03-23	criteria provided, single submitter	clinical testing	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)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000034714	SCV002009618	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001010760	SCV002538544	likely benign	Hereditary cancer-predisposing syndrome	2020-11-09	criteria provided, single submitter	curation
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034714	SCV000043405	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.