ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.2002-4_2002-3del

dbSNP: rs786203664
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167074 SCV000217902 uncertain significance Hereditary cancer-predisposing syndrome 2015-08-10 criteria provided, single submitter clinical testing <p style="text-align:justify">The c.2002-4_2002-3delTC intronic variant is located three nucleotides before coding exon 18 of the NF1 gene. This variant results from a deletion of twonucleotides at positionsc.2002-3 andc.2002-4.Based on data from the NHLBI Exome Sequencing Project(ESP), thisallele has an overall frequency of approximately 0.01% (1/12518) total alleles studied and 0.01% (1/8254) EuropeanAmerican alleles.Allele frequency datafor this varaint are not currently available from the 1000 Genomes Project and the alteration is not currently listed in the Database of Single NucleotidePolymorphisms (dbSNP). To date, this alteration has been detected with an allele frequency of approximately 0.003% (>30000 alleles tested) in our clinical cohort.Thesenucleotide positions arenot well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the nativesplice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of c.2002-4_2002-3delTC remains unclear.
Invitae RCV000476620 SCV000542021 likely benign Neurofibromatosis, type 1 2023-12-02 criteria provided, single submitter clinical testing
GeneDx RCV001753570 SCV002006080 uncertain significance not provided 2019-07-08 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Genetic Services Laboratory, University of Chicago RCV001818397 SCV002065271 uncertain significance not specified 2021-05-14 criteria provided, single submitter clinical testing DNA sequence analysis of the NF1 gene demonstrated a two-nucleotide deletion in intron 17, c.2002-4_2002-3del. This change does not appear to have been previously described in individuals with NF1-related disorders, however, a sequence change at a similar position (c.2002-3C>G) has been described in one family with spinal neurofibromatosis (PMID: 23812910). The c.2002-4_2002-3del sequence change has been described in one non-Finnish European the gnomAD population database (dbSNP rs1363607538). This sequence change is not clearly predicted to have a deleterious effect on splicing based on in silico splice prediction programs. It is possible that this sequence change represents a benign sequence change in the NF1 gene that has not been identified to date. The functional significance of this sequence change is not known at present and its contribution to this patient's disease phenotype cannot definitively be determined.
Ambry Genetics RCV002415713 SCV002721698 likely benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2020-02-26 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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