ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1702_1703del (p.Arg568fs)

gnomAD frequency: 0.00001  dbSNP: rs755032702
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000808513 SCV000948623 uncertain significance Neurofibromatosis, type 2 2023-12-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg568Glyfs*10) in the NF2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 28 amino acid(s) of the NF2 protein. This variant is present in population databases (rs755032702, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with medulloblastoma (PMID: 29489754). ClinVar contains an entry for this variant (Variation ID: 652858). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 RCV002397656 SCV002710166 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-14 criteria provided, single submitter clinical testing The c.1702_1703delAG variant, located in coding exon 15 of the NF2 gene, results from a deletion of two nucleotides at nucleotide positions 1702 to 1703, causing a translational frameshift with a predicted alternate stop codon (p.R568Gfs*10). This alteration occurs at the 3' terminus of theNF2 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 28 amino acids of the protein. The exact functional effect of this alteration is unknown. One study reported this alteration in a pediatric patient diagnosed with a CNS tumor (Gröbner SN et al. Nature. 2018 03;555:321-327). This alteration was also detected in conjunction with an MLH1 pathogenic alteration in a patient undergoing paired somatic and germline testing for hereditary cancer risk via a multigene panel (Cheng DT et al. BMC Med Genomics. 2017 05;10:33). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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