ClinVar Miner

Submissions for variant NM_006206.6(PDGFRA):c.1388C>G (p.Thr463Ser)

gnomAD frequency: 0.00006  dbSNP: rs375047532
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000229738 SCV000289158 likely benign Gastrointestinal stromal tumor 2024-01-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV001011216 SCV001171513 benign Hereditary cancer-predisposing syndrome 2023-04-03 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.
GeneDx RCV002254919 SCV002526191 uncertain significance not provided 2024-04-03 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals from one family with melanoma and sarcoma, some of whom also carried a variant in CDKN2A (PMID: 28592523); This variant is associated with the following publications: (PMID: 28592523)
Sema4, Sema4 RCV001011216 SCV002538547 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-23 criteria provided, single submitter curation
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003325195 SCV004031245 uncertain significance Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal 2023-07-25 criteria provided, single submitter clinical testing The PDGFRA c.1388C>G (p.Thr463Ser) missense change has a maximum subpopulation frequency of 0.068% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with PDGFRA-related conditions. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
PreventionGenetics, part of Exact Sciences RCV003401180 SCV004106073 uncertain significance PDGFRA-related disorder 2024-07-18 no assertion criteria provided clinical testing The PDGFRA c.1388C>G variant is predicted to result in the amino acid substitution p.Thr463Ser. This variant was reported in an individual with sarcoma (Jouenne et al. 2017. PubMed ID: 28592523). This variant is reported in 0.069% of alleles in individuals of South Asian descent in gnomAD and has conflicting interpretations of pathogenicity in ClinVar ranging from likely benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/240305/). Although we suspect that this variant may be benign, 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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