NF2
NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor, the group of A-kinase anchoring proteins|FERM domain containing
Basic information
Region (hg38): 22:29603553-29698598
Links
Phenotypes
GenCC
Source:
- neurofibromatosis type 2 (Strong), mode of inheritance: AD
- familial meningioma (Limited), mode of inheritance: Unknown
- neurofibromatosis type 2 (Definitive), mode of inheritance: AD
- neurofibromatosis type 2 (Supportive), mode of inheritance: AD
- neurofibromatosis type 2 (Definitive), mode of inheritance: AD
- neurofibromatosis type 2 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Schwannomatosis, vestibular (Neurofibromatosis type II) | AD | Oncologic | In order to detect neoplasms (individuals are predisposed to a variety of types of central nervous system tumors), surveillance with regular cranial MRI is indicated, which may allow detection and treatment; In the treatment of neoplasms, radiation therapy should be avoided (especially in childhood) due to the risk of causing or accelerating other neoplasms | Oncologic | 5304294; 4990044; 1479599; 1479598; 8379998; 7913580; 7747758; 8188242; 8751853; 8755919; 9399891; 9643284; 9811917; 9817927; 9863591; 10569966; 10220142; 9874852; 10771486; 11159946; 11342693; 11425952; 12136076; 12235555; 12473765; 12011146; 12566519; 15190457; 15235024; 15831594; 15994874; 16341811; 16521120; 16534111; 16983642; 19476995; 19880713; 20301380; 21451418; 21358190; 22038540; 22098617; 22929112; 22931905; 22989157; 23682341; 23921933; 23931824; 23939548 |
ClinVar
This is a list of variants' phenotypes submitted to
- Neurofibromatosis, type 2 (148 variants)
- Hereditary cancer-predisposing syndrome (27 variants)
- not provided (24 variants)
- Schwannomatosis 1 (2 variants)
- NF2-related disorder (2 variants)
- Spindle cell sarcoma (1 variants)
- Familial meningioma (1 variants)
- Meningioma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NF2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 359 | 365 | ||||
| missense | 736 | 744 | ||||
| nonsense | 65 | 67 | ||||
| start loss | 4 | |||||
| frameshift | 65 | 77 | ||||
| inframe indel | 15 | 16 | ||||
| splice donor/acceptor (+/-2bp) | 41 | 21 | 65 | |||
| splice region | 1 | 1 | 54 | 67 | 1 | 124 |
| non coding | 135 | 221 | 60 | 416 | ||
| Total | 173 | 32 | 903 | 585 | 61 |
Variants in NF2
This is a list of pathogenic ClinVar variants found in the NF2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 22-29603597-A-G | Neurofibromatosis, type 2 | Uncertain significance (Jan 12, 2018) | ||
| 22-29603602-C-T | Neurofibromatosis, type 2 | Uncertain significance (Jan 13, 2018) | ||
| 22-29603679-C-T | Neurofibromatosis, type 2 | Uncertain significance (Jun 14, 2016) | ||
| 22-29603715-C-A | Neurofibromatosis, type 2 | Uncertain significance (Jun 14, 2016) | ||
| 22-29603731-G-T | Neurofibromatosis, type 2 | Uncertain significance (Jan 13, 2018) | ||
| 22-29603753-C-G | Neurofibromatosis, type 2 | Benign (Jan 13, 2018) | ||
| 22-29603754-C-G | Neurofibromatosis, type 2 | Benign (Jan 13, 2018) | ||
| 22-29603795-C-A | Neurofibromatosis, type 2 | Benign (Jun 19, 2018) | ||
| 22-29603836-C-T | Neurofibromatosis, type 2 | Uncertain significance (Jan 12, 2018) | ||
| 22-29603853-TG-T | Neurofibromatosis, type 2 | Uncertain significance (Jul 02, 2018) | ||
| 22-29603889-G-C | Neurofibromatosis, type 2 | Benign (Jun 24, 2018) | ||
| 22-29603933-AG-A | Neurofibromatosis, type 2 | Uncertain significance (Dec 26, 2023) | ||
| 22-29603981-G-A | not specified • Neurofibromatosis, type 2 | Benign/Likely benign (Jul 07, 2023) | ||
| 22-29603994-G-A | Hereditary cancer-predisposing syndrome | Uncertain significance (Feb 22, 2023) | ||
| 22-29603994-G-T | Hereditary cancer-predisposing syndrome • Neurofibromatosis, type 2 | Uncertain significance (Aug 15, 2023) | ||
| 22-29603995-CG-AA | Hereditary cancer-predisposing syndrome | Uncertain significance (May 08, 2024) | ||
| 22-29603995-CGCCATGGCCGGG-C | Neurofibromatosis, type 2 | Uncertain significance (Jul 20, 2023) | ||
| 22-29603998-C-T | Hereditary cancer-predisposing syndrome | Uncertain significance (Oct 19, 2020) | ||
| 22-29603999-A-G | Neurofibromatosis, type 2 | Conflicting classifications of pathogenicity (Mar 26, 2024) | ||
| 22-29604000-T-C | Uncertain significance (May 08, 2023) | |||
| 22-29604001-G-A | Hereditary cancer-predisposing syndrome | Uncertain significance (Nov 17, 2022) | ||
| 22-29604002-G-T | Schwannomatosis 1 • Neurofibromatosis, type 2 • Familial meningioma | Uncertain significance (Apr 27, 2019) | ||
| 22-29604004-C-T | Neurofibromatosis, type 2 | Likely benign (Jun 05, 2019) | ||
| 22-29604004-CG-C | Neurofibromatosis, type 2 | Pathogenic (Apr 10, 2022) | ||
| 22-29604005-G-C | Familial meningioma • Neurofibromatosis, type 2 | Uncertain significance (Jan 12, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NF2 | protein_coding | protein_coding | ENST00000338641 | 16 | 95043 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.00000443 | 125744 | 0 | 3 | 125747 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.29 | 208 | 324 | 0.642 | 0.0000193 | 3952 |
| Missense in Polyphen | 48 | 109.29 | 0.43919 | 1418 | ||
| Synonymous | 0.126 | 123 | 125 | 0.986 | 0.00000799 | 1057 |
| Loss of Function | 5.44 | 0 | 34.5 | 0.00 | 0.00000176 | 416 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000615 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. {ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:21167305}.;
- Disease
- DISEASE: Neurofibromatosis 2 (NF2) [MIM:101000]: Genetic disorder characterized by bilateral vestibular schwannomas (formerly called acoustic neuromas), schwannomas of other cranial and peripheral nerves, meningiomas, and ependymomas. It is inherited in an autosomal dominant fashion with full penetrance. Affected individuals generally develop symptoms of eighth-nerve dysfunction in early adulthood, including deafness and balance disorder. Although the tumors of NF2 are histologically benign, their anatomic location makes management difficult, and patients suffer great morbidity and mortality. {ECO:0000269|PubMed:10090912, ECO:0000269|PubMed:10669747, ECO:0000269|PubMed:10790209, ECO:0000269|PubMed:12709270, ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:20445339, ECO:0000269|PubMed:7666400, ECO:0000269|PubMed:7759081, ECO:0000269|PubMed:7913580, ECO:0000269|PubMed:8081368, ECO:0000269|PubMed:8230593, ECO:0000269|PubMed:8566958, ECO:0000269|PubMed:8698340, ECO:0000269|PubMed:9643284}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Schwannomatosis 1 (SWNTS1) [MIM:162091]: A cancer syndrome in which patients develop multiple non-vestibular schwannomas, benign neoplasms that arise from Schwann cells of the cranial, peripheral, and autonomic nerves. {ECO:0000269|PubMed:18072270}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mesothelioma, malignant (MESOM) [MIM:156240]: An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle- shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. {ECO:0000269|PubMed:12136076}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
- Pathway
- Tight junction - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Hippo signaling pathway - multiple species - Homo sapiens (human);miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Ectoderm Differentiation;Signal Transduction;Fcgamma receptor (FCGR) dependent phagocytosis;Innate Immune System;Immune System;RHO GTPases activate PAKs;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of actin dynamics for phagocytic cup formation;ErbB2/ErbB3 signaling events
(Consensus)
Recessive Scores
- pRec
- 0.357
Intolerance Scores
- loftool
- 0.00841
- rvis_EVS
- -0.87
- rvis_percentile_EVS
- 10.65
Haploinsufficiency Scores
- pHI
- 0.975
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.651
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.688
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nf2
- Phenotype
- nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; endocrine/exocrine gland phenotype; neoplasm; craniofacial phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- nf2b
- Affected structure
- hepatocyte
- Phenotype tag
- abnormal
- Phenotype quality
- increased distance
Gene ontology
- Biological process
- mesoderm formation;negative regulation of cell-matrix adhesion;negative regulation of protein kinase activity;ectoderm development;negative regulation of cell population proliferation;Schwann cell proliferation;regulation of gliogenesis;hippocampus development;negative regulation of cell-cell adhesion;actin cytoskeleton organization;negative regulation of cell migration;regulation of protein stability;regulation of hippo signaling;odontogenesis of dentin-containing tooth;negative regulation of tyrosine phosphorylation of STAT protein;regulation of apoptotic process;negative regulation of MAPK cascade;cell-cell junction organization;positive regulation of cell differentiation;negative regulation of JAK-STAT cascade;positive regulation of stress fiber assembly;regulation of cell cycle;lens fiber cell differentiation;regulation of stem cell proliferation;regulation of protein localization to nucleus;regulation of neural precursor cell proliferation
- Cellular component
- nucleus;nucleolus;cytoplasm;early endosome;cytosol;cytoskeleton;plasma membrane;adherens junction;membrane;lamellipodium;cortical actin cytoskeleton;filopodium membrane;cleavage furrow;ruffle membrane;neuron projection;cell body;apical part of cell;perinuclear region of cytoplasm
- Molecular function
- actin binding;protein binding