ClinVar Miner

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

dbSNP: rs1131691089
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492183 SCV000581277 pathogenic Hereditary cancer-predisposing syndrome 2015-06-02 criteria provided, single submitter clinical testing The c.3198-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 25 in the NF1 gene. This mutation was seen in a 17 year old female who met NIH diagnostic criteria for NF1 andhad aplexiformneurofibromaremoved from her foot at age 16(UpadhyayaM, et al.Hum.Mutat. 2008;29(8):E103-11). In addition, thismutation was reportedin an individualclinically diagnosed with NF1 in a French cohort.RNA studies fromthis publication showed that this splice site mutationinactivatesthe authentic 3' splice site and activates use ofa cryptic site inexon25(also known as exon 19b)(Sabbagh A, et al. Hum. Mutat. 2013;34(11):1510-8).Based on the supporting evidence, c.3198-2A>Gis interpreted as a disease-causing mutation.
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000660029 SCV000781976 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000660029 SCV001407033 pathogenic Neurofibromatosis, type 1 2023-12-12 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 24 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with neurofibromatosis type 1 (PMID: 23913538, 30014477, 31730495). ClinVar contains an entry for this variant (Variation ID: 428967). Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 23913538). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000660029 SCV001479130 pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000660029 SCV002559938 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002489203 SCV002787690 likely pathogenic Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2022-01-31 criteria provided, single submitter clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV000660029 SCV004805520 uncertain significance Neurofibromatosis, type 1 2024-03-25 criteria provided, single submitter research

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