ClinVar Miner

Submissions for variant NM_006206.6(PDGFRA):c.1057A>C (p.Asn353His)

gnomAD frequency: 0.00003  dbSNP: rs139103850
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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 RCV000694495 SCV000822944 uncertain significance Gastrointestinal stromal tumor 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 353 of the PDGFRA protein (p.Asn353His). This variant is present in population databases (rs139103850, gnomAD 0.02%). 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: 135027). 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.
Ambry Genetics RCV002399488 SCV002712488 benign Hereditary cancer-predisposing syndrome 2024-10-02 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 RCV003236780 SCV003935379 uncertain significance not provided 2024-11-05 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on 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)
PreventionGenetics, part of Exact Sciences RCV003407521 SCV004107175 uncertain significance PDGFRA-related disorder 2023-08-18 criteria provided, single submitter clinical testing The PDGFRA c.1057A>C variant is predicted to result in the amino acid substitution p.Asn353His. It has been reported in an individual from a genome sequencing cohort of healthy individuals (Table S1, Bodian et al. 2014. PubMed ID: 24728327). This variant is reported in 0.024% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-55133844-A-C). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/135027/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003444204 SCV004171483 uncertain significance Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal 2023-10-18 criteria provided, single submitter clinical testing The PDGFRA c.1057A>C (p.Asn353His) missense change has a maximum subpopulation frequency of 0.024% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. 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.
ITMI RCV000121799 SCV000085997 not provided not specified 2013-09-19 no assertion provided reference population

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