ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3198-2A>C

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003494720 SCV004297462 pathogenic Neurofibromatosis, type 1 2023-05-05 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 24 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). Disruption of this splice site has been observed in individual(s) with neurofibromatosis type 1 (PMID: 22190595). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004999968 SCV005624563 uncertain significance not provided 2024-10-14 criteria provided, single submitter clinical testing The NF1 c.3198-2A>C variant disrupts a canonical splice-acceptor site and is predicted to interfere with normal NF1 mRNA splicing. However, further research is needed to rule out exon skipping that would maintain the reading frame of the coding sequence. This variant has been reported in the published literature in a family affected with neurofibromatosis type I (PMID: 22190595 (2012)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, we are unable to determine the clinical significance of this variant.

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