ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1522G>A (p.Asp508Asn)

gnomAD frequency: 0.00001  dbSNP: rs749326764
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001012002 SCV001172400 benign Hereditary cancer-predisposing syndrome 2022-11-21 criteria provided, single submitter clinical testing This alteration is classified as 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.
Invitae RCV001340322 SCV001534126 uncertain significance Neurofibromatosis, type 2 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 508 of the NF2 protein (p.Asp508Asn). This variant is present in population databases (rs749326764, gnomAD 0.006%). 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: 819446). 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.
Genome-Nilou Lab RCV001340322 SCV002044899 uncertain significance Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing
GeneDx RCV003238825 SCV003936640 uncertain significance not provided 2022-12-29 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 11756419, 27284491)

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