ClinVar Miner

Submissions for variant NM_005518.4(HMGCS2):c.851C>G (p.Ala284Gly)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003078695 SCV003476059 uncertain significance 3-hydroxy-3-methylglutaryl-CoA synthase deficiency 2022-01-11 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 284 of the HMGCS2 protein (p.Ala284Gly). 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. This variant has not been reported in the literature in individuals affected with HMGCS2-related conditions. This variant is present in population databases (rs201182715, gnomAD 0.002%).
Ambry Genetics RCV003161759 SCV003889917 uncertain significance Inborn genetic diseases 2023-03-02 criteria provided, single submitter clinical testing The c.851C>G (p.A284G) alteration is located in exon 5 (coding exon 5) of the HMGCS2 gene. This alteration results from a C to G substitution at nucleotide position 851, causing the alanine (A) at amino acid position 284 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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