ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1619A>G (p.Asn540Ser)

gnomAD frequency: 0.00004  dbSNP: rs774824164
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000685036 SCV000812507 uncertain significance Neurofibromatosis, type 2 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 540 of the NF2 protein (p.Asn540Ser). This variant is present in population databases (rs774824164, gnomAD 0.01%). 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: 565467). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NF2 protein function with a negative predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV000765630 SCV000896955 uncertain significance Familial meningioma; Neurofibromatosis, type 2; Schwannomatosis 1 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001012452 SCV001172904 likely benign Hereditary cancer-predisposing syndrome 2020-12-29 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.
Genome-Nilou Lab RCV000685036 SCV002044904 uncertain significance Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001012452 SCV002528186 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-12 criteria provided, single submitter curation

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