ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.7062+1G>A

dbSNP: rs863224492
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000200806 SCV000253830 pathogenic Neurofibromatosis, type 1 2022-11-15 criteria provided, single submitter clinical testing Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 (PMID: 17311297, 26740943). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 46 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). ClinVar contains an entry for this variant (Variation ID: 216066). 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.
Ambry Genetics RCV002315627 SCV000663180 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2016-07-28 criteria provided, single submitter clinical testing The c.6999+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 46 of the NF1 gene. This mutation has been reported in at least one individual meeting diagnostic criteria for neurofibromatosis type I (Wimmer K et al. Hum. Mutat., 2007 Jun;28:599-612). Using two different splice site prediction tools, this alteration is predicted to abolish the native splice donor site and to significantly weaken (but not abolish) the efficiency of the native splice donor site by BDGP and ESEfinder, respectively; 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 pathogenic.
Genome-Nilou Lab RCV000200806 SCV002560229 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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