Submissions for variant NM_003072.5(SMARCA4):c.2617-1G>A

dbSNP: rs1600277713

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001856208	SCV002282538	likely pathogenic	Rhabdoid tumor predisposition syndrome 2	2020-11-22	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. 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 SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 635378). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 18 of the SMARCA4 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 SMARCA4 are known to be pathogenic (PMID: 24658001, 24658002).
MutSpliceDB: a database of splice sites variants effects on splicing, NIH	RCV000786805	SCV000925697	not provided	not provided		no assertion provided	in vitro