Submissions for variant NM_001127222.2(CACNA1A):c.4089+1G>A

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002995481	SCV003294041	likely pathogenic	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2022-07-25	criteria provided, single submitter	clinical testing	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. This sequence change affects a donor splice site in intron 25 of the CACNA1A 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), and loss-of-function variants in CACNA1A are known to be pathogenic (PMID: 10371528, 19486177, 25735478, 27250579). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust	RCV004007746	SCV004814221	pathogenic	Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 42	2021-01-08	criteria provided, single submitter	clinical testing	Criteria Codes: PVS1 PM2