ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5269-14C>G

dbSNP: rs753463683
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UAB Medical Genomics Laboratory, UAB Medicine RCV001007750 SCV001167429 pathogenic Neurofibromatosis, type 1 2020-01-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001007750 SCV002254854 pathogenic Neurofibromatosis, type 1 2022-08-31 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 32126153). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 561680). This variant has been observed in individual(s) with clinical features of neurofibromatosis type 1 and/or neurofibromatosis type 1 (PMID: 32126153; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 36 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product.
MGZ Medical Genetics Center RCV001007750 SCV002581707 likely pathogenic Neurofibromatosis, type 1 2022-08-08 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001007750 SCV004027713 likely pathogenic Neurofibromatosis, type 1 2023-07-03 criteria provided, single submitter clinical testing Criteria applied: PS3_MOD,PS4_MOD,PM2_SUP,PP3,PP4
GeneDx RCV000681028 SCV000808480 uncertain significance not provided 2018-08-10 flagged submission clinical testing The c.5206-14 C>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is not observed in large population cohorts (Lek et al., 2016). Several in silico splice prediction models predict that c.5206-14 C>G creates a cryptic acceptor site which may supplant the natural acceptor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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