ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.3990-2A>G

dbSNP: rs1057524483
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000427802 SCV000535688 pathogenic not provided 2024-04-23 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD)
Labcorp Genetics (formerly Invitae), Labcorp RCV001377005 SCV001574221 likely pathogenic Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2020-10-08 criteria provided, single submitter clinical testing Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CACNA1A are known to be pathogenic (PMID: 10371528, 19486177, 25735478, 27250579). 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. 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. This variant has been observed in individual(s) with clinical features of CACNA1A-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 392420). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 24 of the CACNA1A gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

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