ClinVar Miner

Submissions for variant NM_032634.4(PIGO):c.2405G>A (p.Arg802Gln)

gnomAD frequency: 0.00001  dbSNP: rs771347652
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498401 SCV000590635 uncertain significance not provided 2017-06-16 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the PIGO gene. The R802Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R802Q variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R802Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals; however Glutamine has been seen at this position in evolution. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001360357 SCV001556271 uncertain significance Hyperphosphatasia with intellectual disability syndrome 2 2022-08-09 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 802 of the PIGO protein (p.Arg802Gln). This variant is present in population databases (rs771347652, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with PIGO-related conditions. ClinVar contains an entry for this variant (Variation ID: 432865). 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. 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.

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