ClinVar Miner

Submissions for variant NM_198903.2(GABRG2):c.245G>A (p.Arg82Gln) (rs121909673)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187520 SCV000241114 pathogenic not provided 2018-07-03 criteria provided, single submitter clinical testing p.Arg82Gln (R82Q) CGG>CAG: c.245 G>A in exon 2 of the GABRG2 gene (NM_000816.3) The R82Q missense variant (reported as R43Q due to alternate nomenclature) segregated with childhood absence epilepsy and/or febrile seizures in many affected individuals from a single large family (Wallace et al., 2001; Marini et al., 2003). Functional studies indicate the variant disrupts GABA-A receptor assembly and reduces receptor current density and current amplitude (Huang et al., 2014; Bianchi et al., 2002). This variant is not observed in large population cohorts (Lek et al., 2016). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. We interpret the R82Q variant as pathogenic. The variant is found in EPILEPSY panel(s).
Invitae RCV000645380 SCV000767125 likely pathogenic Epilepsy, childhood absence 2; Familial febrile seizures 8 2017-11-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 82 of the GABRG2 protein (p.Arg82Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with childhood absence epilepsy and/or febrile seizures in a large family (PMID: 11326275) In addition, it has also been reported in several individuals affected with febrile seizures (PMID: 24630281). This variant is also known as R43Q in the literature. ClinVar contains an entry for this variant (Variation ID: 16208). Experimental studies have shown that this missense change impairs GABA type A receptor function by abolishing the surface expression of the GABRG2 proteins and results in the reduction of synaptic inhibition and neuronal hyperexcitability (PMID: 11326275, 18094250, 25731747, 15470132, 15866052, 12097483, 16510738). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000017592 SCV000037864 risk factor Epilepsy, childhood absence 2 2013-09-27 no assertion criteria provided literature only
OMIM RCV000017593 SCV000037865 pathogenic Familial febrile seizures 8 2013-09-27 no assertion criteria provided literature only

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