ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.675+4T>C

gnomAD frequency: 0.00001  dbSNP: rs1306740609
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001944405 SCV002214312 uncertain significance Neurofibromatosis, type 2 2023-09-23 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the NF2 gene. It does not directly change the encoded amino acid sequence of the NF2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with NF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1433382). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Ambry Genetics RCV003303446 SCV004000087 benign Hereditary cancer-predisposing syndrome 2023-05-15 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
All of Us Research Program, National Institutes of Health RCV001944405 SCV004837223 uncertain significance Neurofibromatosis, type 2 2024-02-05 criteria provided, single submitter clinical testing This variant causes a T to C nucleotide substitution at the +4 position of intron 7 of the NF2 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with NF2-related disorders in the literature. This variant has been identified in 3/251438 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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