ClinVar Miner

Submissions for variant NM_005458.8(GABBR2):c.1662+1G>A

dbSNP: rs1832058906
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001323231 SCV001514139 uncertain significance Epileptic encephalopathy 2024-07-29 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 11 of the GABBR2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in GABBR2 cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GABBR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1023217). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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.
Revvity Omics, Revvity RCV003130269 SCV003816248 uncertain significance not provided 2021-10-29 criteria provided, single submitter clinical testing
Clinical Genomics Laboratory, Washington University in St. Louis RCV003458669 SCV004177079 uncertain significance Neurodevelopmental disorder with poor language and loss of hand skills; Developmental and epileptic encephalopathy, 59 2023-07-21 criteria provided, single submitter clinical testing The GABBR2 c.1662+1G>A variant, to our knowledge, has not been reported in the medical literature but has been reported in the ClinVar database as a germline variant of uncertain significance by two submitters. This variant is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant occurs within the canonical splice donor site, which is predicted to cause skipping of the exon, leading to an out of frame transcript. However, loss of function is not the known disease mechanism. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.
GeneDx RCV003130269 SCV005628846 uncertain significance not provided 2024-07-16 criteria provided, single submitter clinical testing Canonical splice site variant in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge

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