Submissions for variant NM_006206.6(PDGFRA):c.46A>T (p.Thr16Ser)

gnomAD frequency: 0.00001  dbSNP: rs587778596

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000461163	SCV000546582	uncertain significance	Gastrointestinal stromal tumor	2024-01-09	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 16 of the PDGFRA protein (p.Thr16Ser). This variant is present in population databases (rs587778596, gnomAD 0.003%). 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: 135017). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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	RCV001022920	SCV001184716	uncertain significance	Hereditary cancer-predisposing syndrome	2019-01-02	criteria provided, single submitter	clinical testing	The p.T16S variant (also known as c.46A>T), located in coding exon 1 of the PDGFRA gene, results from an A to T substitution at nucleotide position 46. The threonine at codon 16 is replaced by serine, an amino acid with similar properties. This variant was identified in a cohort of 681 ancestrally diverse, healthy subjects. (Bodian DL et al. PLoS ONE. 2014 Apr;9:e94554). This amino acid position is not 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	RCV003128582	SCV003805839	uncertain significance	not provided	2022-08-24	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); 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; This variant is associated with the following publications: (PMID: 24728327)
CeGaT Center for Human Genetics Tuebingen	RCV003128582	SCV003916896	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	PDGFRA: BP4
ITMI	RCV000121786	SCV000085984	not provided	not specified	2013-09-19	no assertion provided	reference population