ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1446G>A (p.Pro482=)

gnomAD frequency: 0.00001  dbSNP: rs753751373
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460735 SCV000553684 uncertain significance Neurofibromatosis, type 2 2024-01-04 criteria provided, single submitter clinical testing This sequence change affects codon 482 of the NF2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NF2 protein. This variant also falls at the last nucleotide of exon 13, which is part of the consensus splice site for this exon. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 412215). 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 (Invitae). 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 RCV002393165 SCV002697921 likely benign Hereditary cancer-predisposing syndrome 2020-02-06 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.
Baylor Genetics RCV003470520 SCV004191313 uncertain significance Familial meningioma 2023-04-21 criteria provided, single submitter clinical testing

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