Submissions for variant NM_002294.3(LAMP2):c.65-1G>C

dbSNP: rs730880496

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000157989	SCV000207924	pathogenic	not provided	2023-11-05	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); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15673802, 26748608)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001208408	SCV001379792	likely pathogenic	Danon disease	2025-01-20	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 1 of the LAMP2 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 LAMP2 are known to be pathogenic (PMID: 21415759). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 180891). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.