ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3871-2A>G

dbSNP: rs1131691077
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492202 SCV000581257 pathogenic Hereditary cancer-predisposing syndrome 2014-10-09 criteria provided, single submitter clinical testing The c.3871-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 29 of the NF1 gene. This mutation has been detected in an individual meeting NIH diagnostic criteria for Neurofibromatosis type 1 (NF1) and is predicted at the mRNA level to induce the skipping of exon 23 (r.3871_3974del104) (Sabbagh A et al. Hum. Mutat., 2013 Nov;34:1510-8). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV000560336 SCV000628552 pathogenic Neurofibromatosis, type 1 2024-01-26 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 28 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 (PMID: 21520333, 23913538; Invitae). ClinVar contains an entry for this variant (Variation ID: 428953). 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 RCV000560336 SCV002560003 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002356808 SCV002620517 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2020-04-10 criteria provided, single submitter clinical testing The c.3871-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 29 of the NF1 gene. This mutation has been detected in an individual meeting NIH diagnostic criteria for Neurofibromatosis type 1 (NF1) and is predicted at the mRNA level to induce the skipping of exon 23 (r.3871_3974del104) (Sabbagh A et al. Hum. Mutat., 2013 Nov;34:1510-8). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
GeneDx RCV004800427 SCV005421418 pathogenic not provided 2024-06-03 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); This variant is associated with the following publications: (PMID: 16199547, 10712197, 23913538, 31573083)

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