ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1392+1G>A

dbSNP: rs267604791
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000497249 SCV000781904 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002318952 SCV001171603 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2018-04-04 criteria provided, single submitter clinical testing The c.1392+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 12 of the NF1 gene. This alteration has been detected in three individuals with neurofibromatosis type 1 (NF1), including two affected siblings (Trevisson E et al. Clin. Genet., 2014 Apr;85:386-9; De Luca A et al. Hum. Mutat., 2004 Jun;23:629). Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site. Further in vitro analysis by PCR-RFLP assay also demonstrated that this alteration abolishes the native splice donor site (Trevisson E et al. Clin. Genet., 2014 Apr;85:386-9). 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.
Genome-Nilou Lab RCV000497249 SCV002561660 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000497249 SCV003441785 pathogenic Neurofibromatosis, type 1 2024-02-17 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 12 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 individual(s) with neurofibromatosis type 1 (PMID: 15146469, 23621909). ClinVar contains an entry for this variant (Variation ID: 80403). 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.
Medical Genetics, University of Parma RCV000497249 SCV000588717 likely pathogenic Neurofibromatosis, type 1 2017-02-02 no assertion criteria provided clinical testing

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