ClinVar Miner

Submissions for variant NM_207122.2(EXT2):c.1412G>A (p.Arg471Gln)

gnomAD frequency: 0.00006  dbSNP: rs141256266
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001363071 SCV001559160 uncertain significance Exostoses, multiple, type 2 2024-09-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 471 of the EXT2 protein (p.Arg471Gln). This variant is present in population databases (rs141256266, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of EXT2-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 1054549). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt EXT2 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 RCV002547808 SCV003724828 uncertain significance Inborn genetic diseases 2022-11-09 criteria provided, single submitter clinical testing The c.1412G>A (p.R471Q) alteration is located in exon 9 (coding exon 8) of the EXT2 gene. This alteration results from a G to A substitution at nucleotide position 1412, causing the arginine (R) at amino acid position 471 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003946025 SCV004763921 uncertain significance EXT2-related disorder 2023-11-16 no assertion criteria provided clinical testing The EXT2 c.1412G>A variant is predicted to result in the amino acid substitution p.Arg471Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0087% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-44219485-G-A) and has been interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1054549/). 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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