ClinVar Miner

Submissions for variant NM_015141.4(GPD1L):c.853-2A>G

dbSNP: rs766733448
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002023415 SCV002306974 uncertain significance Brugada syndrome 2021-11-04 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 6 of the GPD1L 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 GPD1L cause disease. 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 disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with GPD1L-related conditions.
Fulgent Genetics, Fulgent Genetics RCV002492379 SCV002792712 uncertain significance Brugada syndrome 2 2021-09-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV003161253 SCV003859621 uncertain significance Cardiovascular phenotype 2023-01-04 criteria provided, single submitter clinical testing The c.853-2A>G intronic variant results from an A to G substitution two nucleotides before coding exon 7 in the GPD1L gene. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, loss of function of GPD1L has not been established as a mechanism of disease. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.

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