ClinVar Miner

Submissions for variant NM_002063.4(GLRA2):c.754C>T (p.Arg252Cys)

gnomAD frequency: 0.00001  dbSNP: rs748764171
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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 RCV003728017 SCV004534902 uncertain significance not provided 2022-11-12 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. Experimental studies have shown that this missense change affects GLRA2 function (PMID: 35294868). 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 expected to disrupt GLRA2 protein function. ClinVar contains an entry for this variant (Variation ID: 1334405). This missense change has been observed in individual(s) with GLRA2-related conditions (PMID: 35294868). This variant is present in population databases (rs748764171, gnomAD 0.001%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 252 of the GLRA2 protein (p.Arg252Cys).
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV002246530 SCV004806941 uncertain significance Intellectual developmental disorder, X-linked, syndromic, Pilorge type 2024-03-26 criteria provided, single submitter clinical testing
Wangler Lab, Baylor College of Medicine RCV001813916 SCV002056022 uncertain significance See cases 2022-01-10 no assertion criteria provided research Marcogliese et al., (2022) have identified 13 unrelated subjects with a variable neurodevelopmental disorder with or without autistic features. The c.754C>T results in an amino acid change of p.Arg252Cys. This variant was shown to act as Loss of Function in functional studies using Drosophila. This variant was identified in a male proband with maternal inheritance (unaffected mother).
OMIM RCV002246530 SCV002520428 pathogenic Intellectual developmental disorder, X-linked, syndromic, Pilorge type 2022-04-26 no assertion criteria provided literature only

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