Submissions for variant NM_001127222.2(CACNA1A):c.4866+1G>T

dbSNP: rs2144725957

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001377850	SCV001575288	likely pathogenic	Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42	2020-09-15	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. 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). 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 not been reported in the literature in individuals with CACNA1A-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 30 of the CACNA1A gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Institute of Human Genetics, University of Leipzig Medical Center	RCV003322621	SCV004027698	likely pathogenic	Developmental and epileptic encephalopathy, 42	2023-06-13	criteria provided, single submitter	clinical testing	Criteria applied: PVS1_STR,PS4_SUP,PM2_SUP