ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.730+2T>G

dbSNP: rs200962248
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000034588 SCV002013368 pathogenic not provided 2021-05-03 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; Observed in an individual via exome sequencing for cancer-susceptibility syndromes in participants with atherosclerosis phenotypes (Johnston et al., 2012); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 22703879)
Labcorp Genetics (formerly Invitae), Labcorp RCV003597961 SCV004552030 pathogenic Neurofibromatosis, type 1 2023-05-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 41676). Disruption of this splice site has been observed in individuals with NF1-related conditions (PMID: 21354044, 22190595). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change affects a donor splice site in intron 7 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).
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000034588 SCV000043384 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000202947 SCV000257764 benign not specified 2015-06-18 flagged submission clinical testing

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