ClinVar Miner

Submissions for variant NM_002609.4(PDGFRB):c.2705C>T (p.Thr902Ile)

gnomAD frequency: 0.00006  dbSNP: rs200865355
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480759 SCV000572990 uncertain significance not provided 2017-02-10 criteria provided, single submitter clinical testing The T902I variant in the PDGFRB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T902I variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T902I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T902I as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002526658 SCV003247034 uncertain significance Acroosteolysis-keloid-like lesions-premature aging syndrome; Basal ganglia calcification, idiopathic, 4; Infantile myofibromatosis; Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome 2022-10-13 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 423309). This variant has not been reported in the literature in individuals affected with PDGFRB-related conditions. This variant is present in population databases (rs200865355, gnomAD 0.01%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 902 of the PDGFRB protein (p.Thr902Ile).
Ambry Genetics RCV002526657 SCV003682127 likely benign Inborn genetic diseases 2021-09-21 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
Breakthrough Genomics, Breakthrough Genomics RCV000480759 SCV005188688 uncertain significance not provided criteria provided, single submitter not provided

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