Submissions for variant NM_001042492.3(NF1):c.731-2A>G

dbSNP: rs1555608924

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV000992434	SCV001144744	pathogenic	not provided	2019-02-14	criteria provided, single submitter	clinical testing	The variant disrupts a canonical splice site, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Invitae	RCV001207548	SCV001378908	pathogenic	Neurofibromatosis, type 1	2022-08-01	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 7 of the NF1 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 NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 and a diagnosis or suspicion of neurofibromatosis type 1 (PMID: 12746402, 18546366, 19061981). It has also been observed to segregate with disease in related individuals. This variant is also known as IVS5-2A>G. ClinVar contains an entry for this variant (Variation ID: 805084). 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.
Genome-Nilou Lab	RCV001207548	SCV002561601	pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000992434	SCV002585631	pathogenic	not provided	2022-08-01	criteria provided, single submitter	clinical testing	NF1: PVS1, PM2, PP4