Submissions for variant NM_002609.4(PDGFRB):c.2855C>G (p.Ser952Cys)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002933529	SCV003270501	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	2023-10-20	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 952 of the PDGFRB protein (p.Ser952Cys). This variant is present in population databases (rs376007701, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PDGFRB-related conditions. ClinVar contains an entry for this variant (Variation ID: 2059038). 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 PDGFRB protein function. 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.
GeneDx	RCV003324860	SCV004030972	uncertain significance	not provided	2023-02-27	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
PreventionGenetics, part of Exact Sciences	RCV003409970	SCV004106355	uncertain significance	PDGFRB-related disorder	2023-01-31	criteria provided, single submitter	clinical testing	The PDGFRB c.2855C>G variant is predicted to result in the amino acid substitution p.Ser952Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/5-149498359-G-C), which may be too frequent for an undocumented cause of disease. 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.