ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.8113+2T>G

dbSNP: rs1597868312
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002445178 SCV001189619 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2018-01-19 criteria provided, single submitter clinical testing The c.8050+2T>G intronic variant results from a T to G substitution two nucleotides after coding exon 54 in the NF1 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. 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 likely pathogenic.
Invitae RCV001862397 SCV002225283 pathogenic Neurofibromatosis, type 1 2021-11-12 criteria provided, single submitter clinical testing Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (Invitae). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 827420). Disruption of this splice site has been observed in individual(s) with neurofibromatosis type 1 (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 54 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).
Genome-Nilou Lab RCV001862397 SCV002560601 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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