ClinVar Miner

Submissions for variant NM_006206.6(PDGFRA):c.820A>T (p.Thr274Ser)

gnomAD frequency: 0.00007  dbSNP: rs747956260
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000538238 SCV000630680 uncertain significance Gastrointestinal stromal tumor 2024-01-19 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 274 of the PDGFRA protein (p.Thr274Ser). This variant is present in population databases (rs747956260, gnomAD 0.007%). 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: 459124). 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 with a negative predictive value of 80%. 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.
Baylor Genetics RCV004568760 SCV005055148 uncertain significance Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal 2024-02-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV004943958 SCV005470972 benign Hereditary cancer-predisposing syndrome 2024-08-20 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV004745449 SCV005345853 uncertain significance PDGFRA-related disorder 2024-08-14 no assertion criteria provided clinical testing The PDGFRA c.820A>T variant is predicted to result in the amino acid substitution p.Thr274Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of European (Non-Finnish) descent in gnomAD and is reported in ClinVar as a variant of uncertain significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/459124/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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