Submissions for variant NM_000080.4(CHRNE):c.803-2A>G

gnomAD frequency: 0.00002  dbSNP: rs1320610655

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001069955	SCV001235158	pathogenic	Congenital myasthenic syndrome 4A	2023-09-10	criteria provided, single submitter	clinical testing	This variant is also known as IVS7-2A/G. ClinVar contains an entry for this variant (Variation ID: 863073). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. Disruption of this splice site has been observed in individual(s) with autosomal recessive congenital myasthenic syndrome (PMID: 12536367, 28464723). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This sequence change affects an acceptor splice site in intron 7 of the CHRNE 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 CHRNE are known to be pathogenic (PMID: 22678886). This variant is present in population databases (no rsID available, gnomAD 0.004%).
CeGaT Center for Human Genetics Tuebingen	RCV003413893	SCV004139445	pathogenic	not provided	2024-04-01	criteria provided, single submitter	clinical testing	CHRNE: PVS1, PM2, PM3
Baylor Genetics	RCV001069955	SCV004212582	pathogenic	Congenital myasthenic syndrome 4A	2024-01-05	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001828522	SCV002093412	pathogenic	Congenital myasthenic syndrome	2021-01-04	no assertion criteria provided	clinical testing