ClinVar Miner

Submissions for variant NM_005518.4(HMGCS2):c.274C>G (p.Arg92Gly)

gnomAD frequency: 0.00018  dbSNP: rs771955824
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002265482 SCV002547211 uncertain significance not provided 2022-07-08 criteria provided, single submitter clinical testing Missense variants in this gene are often considered pathogenic (HGMD); 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
Labcorp Genetics (formerly Invitae), Labcorp RCV003095999 SCV003251363 uncertain significance 3-hydroxy-3-methylglutaryl-CoA synthase deficiency 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 92 of the HMGCS2 protein (p.Arg92Gly). This variant is present in population databases (rs771955824, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with HMGCS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1695847). 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 tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV003096000 SCV003710084 uncertain significance Inborn genetic diseases 2022-12-01 criteria provided, single submitter clinical testing The c.274C>G (p.R92G) alteration is located in exon 2 (coding exon 2) of the HMGCS2 gene. This alteration results from a C to G substitution at nucleotide position 274, causing the arginine (R) at amino acid position 92 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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