ClinVar Miner

Submissions for variant NM_198903.2(GABRG2):c.549-3T>G (rs750459631)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187524 SCV000241118 uncertain significance not provided 2016-09-09 criteria provided, single submitter clinical testing The c.549-3 T>G variant in the GABRG2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. Several in-silico splice prediction models predict that c.549-3 T>G damages the natural acceptor site of intron 4 and leads to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. The c.549-3 T>G 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). We interpret c.549-3 T>G as a variant of uncertain significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000187524 SCV000493387 likely pathogenic not provided 2016-08-01 criteria provided, single submitter clinical testing
Invitae RCV001234167 SCV001406798 uncertain significance Epilepsy, childhood absence 2; Familial febrile seizures 8 2019-11-06 criteria provided, single submitter clinical testing This sequence change falls in intron 4 of the GABRG2 gene. It does not directly change the encoded amino acid sequence of the GABRG2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs750459631, ExAC 0.006%). This variant has been observed in individual(s) with Rolandic epilepsy (PMID: 25726841, 29358611). ClinVar contains an entry for this variant (Variation ID: 205543). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Bioinformatics Core,Luxembourg Center for Systems Biomedicine RCV000655993 SCV000588269 pathogenic Rolandic epilepsy 2017-01-01 no assertion criteria provided case-control CAADphred>15

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