Submissions for variant NM_001042492.3(NF1):c.888+789A>G

dbSNP: rs1597660974

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000822665	SCV000963475	uncertain significance	Neurofibromatosis, type 1	2018-10-05	criteria provided, single submitter	clinical testing	The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change falls in intron 8 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. This variant has been observed in an individual affected with neurofibromatosis type 1 (NF1) (PMID: 27322474). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies.
GeneDx	RCV003327467	SCV004034843	likely pathogenic	not provided	2023-09-28	criteria provided, single submitter	clinical testing	Published RNA studies demonstrate that this variant causes abnormal splicing (Evans et al., 2016; Douben et al., 2022); No data available from control populations to assess the frequency of this variant; This variant is associated with the following publications: (PMID: Svaasand2015[article], 27322474, 36251260)
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000822665	SCV004099116	pathogenic	Neurofibromatosis, type 1	2023-09-07	criteria provided, single submitter	clinical testing	PS3, PS4, PM2, PM6
PreventionGenetics, part of Exact Sciences	RCV004549901	SCV004111133	uncertain significance	NF1-related disorder	2022-12-29	criteria provided, single submitter	clinical testing	The NF1 c.888+789A>G variant is predicted to interfere with splicing. This variant was reported in an individual diagnosed with Neurofibromatosis 1, and was predicted to impact splicing (Evans et al. 2016. PubMed ID: 27322474). In silico splice prediction algorithms suggest this change may enhance a cryptic splice donor site (Alamut Visual Plus v1.6.1). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
CeGaT Center for Human Genetics Tuebingen	RCV003327467	SCV005330414	likely pathogenic	not provided	2024-08-01	criteria provided, single submitter	clinical testing	NF1: PM2, PS3:Moderate, PS4:Moderate