Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002342443 | SCV002639056 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-29 | criteria provided, single submitter | clinical testing | The p.D154N variant (also known as c.460G>A), located in coding exon 5 of the NF2 gene, results from a G to A substitution at nucleotide position 460. The aspartic acid at codon 154 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003094788 | SCV003011802 | uncertain significance | Neurofibromatosis, type 2 | 2023-09-17 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1741876). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 154 of the NF2 protein (p.Asp154Asn). |
| All of Us Research Program, |
RCV003094788 | SCV004830971 | uncertain significance | Neurofibromatosis, type 2 | 2023-06-26 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with asparagine at codon 154 of the NF2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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 2/251312 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. |
| Baylor Genetics | RCV004572285 | SCV005052365 | uncertain significance | Familial meningioma | 2024-02-19 | criteria provided, single submitter | clinical testing |