ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.6820-2A>G

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory, Motol Hospital RCV004787560 SCV005402672 likely pathogenic Neurofibromatosis, type 1 2024-11-20 criteria provided, single submitter clinical testing This variant was detected in a female with multiple cafe-au-lait spots, mild developmental delay and autistic features. The variant is predicted to disrupt canonical splice acceptor site on the borderline of intron 45 and exon 46. Different nucleotide change is a well-known pathogenic variant: c.6820-2A>C (ClinVar Variation ID: 1048727). The variants affecting the canonical splice donor and acceptor sites of the NF1 gene are well documented as a molecular cause of neurofibromatosis type 1 (OMIM:162200) (PMID:31776437;10607834;23244495;34782607). To conclude, the variant is classified as likely pathogenic (ACMG PVS1, PM2).
Juno Genomics, Hangzhou Juno Genomics, Inc RCV004787560 SCV005416537 likely pathogenic Neurofibromatosis, type 1 criteria provided, single submitter clinical testing PM2_Supporting+PVS1_Strong+PS4_Supporting+PP4+PM6_Supporting
Labcorp Genetics (formerly Invitae), Labcorp RCV004787560 SCV005836534 pathogenic Neurofibromatosis, type 1 2025-01-21 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 44 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: 23668869). 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.

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