ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.2001+4A>G

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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 RCV002417180 SCV002724233 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-09-11 criteria provided, single submitter clinical testing The c.2001+4A>G intronic variant results from an A to G substitution 4 nucleotides after coding exon 17 in the NF1 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003101000 SCV002968629 uncertain significance Neurofibromatosis, type 1 2025-01-12 criteria provided, single submitter clinical testing This sequence change falls in intron 17 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1784243). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). RNA analysis performed to evaluate the impact of this variant on mRNA splicing indicates it does not significantly alter splicing (internal data). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics RCV004572457 SCV005052270 uncertain significance Juvenile myelomonocytic leukemia 2024-01-08 criteria provided, single submitter clinical testing

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