The NF2 c.107A>G variant is predicted to result in the amino acid substitution p.Asn36Ser. This variant was previously described in one individual who presented with suspected neurofibromatosis type 2 (Wallace et al. 2004. PubMed ID: 15684865) and in a patient with a mild form of vestibular schwannomas (Heineman et al. 2015. PubMed ID: 25931164). However, this variant has also been reported in a cohort of presumably healthy individuals (Table S1 - Bodian et al. 2014. PubMed ID: 24728327). This variant is reported in 0.016% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-30000094-A-G) and has conflicting interpretations regarding its pathogenicity in ClinVar, ranging from benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/134892/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
ClinVar Genomic variation as it relates to human health
NM_000268.4(NF2):c.107A>G (p.Asn36Ser)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(11)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Conflicting classifications of pathogenicity
Uncertain significance(6); Benign(1); Likely benign(3)
Uncertain significance(6); Benign(1); Likely benign(3)
11
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000268.4(NF2):c.107A>G (p.Asn36Ser)
Variation ID: 134892 Accession: VCV000134892.34
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 22q12.2 22: 29604105 (GRCh38) [ NCBI UCSC ] 22: 30000094 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jun 9, 2014 Oct 20, 2024 Jan 27, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000268.4:c.107A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000259.1:p.Asn36Ser missense NM_016418.5:c.107A>G NP_057502.2:p.Asn36Ser missense NM_181825.3:c.107A>G NP_861546.1:p.Asn36Ser missense NM_181828.3:c.107A>G NP_861966.1:p.Asn36Ser missense NM_181829.3:c.107A>G NP_861967.1:p.Asn36Ser missense NM_181830.3:c.107A>G NP_861968.1:p.Asn36Ser missense NM_181831.3:c.107A>G NP_861969.1:p.Asn36Ser missense NM_181832.2:c.107A>G NM_181832.3:c.107A>G NP_861970.1:p.Asn36Ser missense NM_181833.3:c.107A>G NP_861971.1:p.Asn36Ser missense NR_156186.2:n.473A>G non-coding transcript variant NC_000022.11:g.29604105A>G NC_000022.10:g.30000094A>G NG_009057.1:g.5550A>G LRG_511:g.5550A>G LRG_511t1:c.107A>G LRG_511p1:p.Asn36Ser LRG_511t2:c.107A>G LRG_511p2:p.Asn36Ser - Protein change
- N36S
- Other names
- -
- Canonical SPDI
- NC_000022.11:29604104:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00020 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 0.00020
1000 Genomes Project 30x 0.00031
The Genome Aggregation Database (gnomAD), exomes 0.00003
Exome Aggregation Consortium (ExAC) 0.00007
Trans-Omics for Precision Medicine (TOPMed) 0.00008
The Genome Aggregation Database (gnomAD) 0.00014
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| NF2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2084 | 2132 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| not provided (1) |
no classification provided
|
Sep 19, 2013 | RCV000121642.2 | |
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Nov 13, 2021 | RCV000564583.6 | |
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Nov 1, 2023 | RCV000733228.20 | |
| Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
|
Jan 27, 2024 | RCV001085689.14 | |
|
NF2-related disorder
|
Uncertain significance (1) |
criteria provided, single submitter
|
Mar 15, 2023 | RCV003398733.4 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Mar 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
NF2-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004120477.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The NF2 c.107A>G variant is predicted to result in the amino acid substitution p.Asn36Ser. This variant was previously described in one individual who presented with … (more)
The NF2 c.107A>G variant is predicted to result in the amino acid substitution p.Asn36Ser. This variant was previously described in one individual who presented with suspected neurofibromatosis type 2 (Wallace et al. 2004. PubMed ID: 15684865) and in a patient with a mild form of vestibular schwannomas (Heineman et al. 2015. PubMed ID: 25931164). However, this variant has also been reported in a cohort of presumably healthy individuals (Table S1 - Bodian et al. 2014. PubMed ID: 24728327). This variant is reported in 0.016% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-30000094-A-G) and has conflicting interpretations regarding its pathogenicity in ClinVar, ranging from benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/134892/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
|
|
|
Uncertain significance
(Apr 03, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Neurofibromatosis, type 2
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003815873.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
|
Uncertain significance
(Nov 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004154847.10
First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 2
|
|
|
Uncertain significance
(May 29, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000861268.1
First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
|
Likely benign
(Mar 26, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001788035.1
First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29618661, 32150022, 23975423, … (more)
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29618661, 32150022, 23975423, 25931164, 25925381, 16983642, 15684865, 24728327) (less)
|
|
|
Likely benign
(Nov 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Neurofibromatosis, type 2
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002045393.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
|
|
|
Uncertain significance
(Nov 13, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002528164.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The NF2 c.107A>G (p.N36S) variant has been reported in heterozygosity in at least two individuals with vestibular schwannomas (PMID: 15684865, 25931164) as well as in … (more)
The NF2 c.107A>G (p.N36S) variant has been reported in heterozygosity in at least two individuals with vestibular schwannomas (PMID: 15684865, 25931164) as well as in several healthy individuals (PMID: 24728327). This variant was observed in 3/18900 chromosomes in the East Asian population according to the Genome Aggregation Database (PMID: 32461654). The variant has been reported in ClinVar (Variation ID 134892). Functional studies have not been performed, and in silico predictions of the variant's effect on protein function are inconclusive. The evidence is insufficient to meet ACMG/AMP criteria for classifying the variant as benign or pathogenic. Thus, the clinical significance of this variant is currently uncertain. (less)
|
|
|
|
Uncertain significance
(Mar 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Neurofibromatosis, type 2
Affected status: unknown
Allele origin:
germline
|
St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV003928057.1
First in ClinVar: Jun 03, 2023 Last updated: Jun 03, 2023 |
Comment:
The NF2 c.107A>G (p.Asn36Ser) missense change has a maximum subpopulation frequency of 0.029% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign … (more)
The NF2 c.107A>G (p.Asn36Ser) missense change has a maximum subpopulation frequency of 0.029% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. This variant has been reported in an individual with a vestibular schwannoma (PMID: 15684865). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. (less)
|
|
|
Benign
(Jan 27, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Neurofibromatosis, type 2
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000284538.9
First in ClinVar: Jul 01, 2016 Last updated: Feb 14, 2024 |
|
|
|
Likely benign
(Dec 14, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000674122.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. (less)
|
|
|
not provided
(Sep 19, 2013)
|
no classification provided
Method: reference population
|
AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
|
ITMI
Accession: SCV000085840.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
|
Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
|
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Comment:
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29618661, 32150022, 23975423, 25931164, 25925381, 16983642, 15684865, 24728327)
Comment:
The NF2 c.107A>G (p.Asn36Ser) missense change has a maximum subpopulation frequency of 0.029% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. This variant has been reported in an individual with a vestibular schwannoma (PMID: 15684865). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
The NF2 c.107A>G variant is predicted to result in the amino acid substitution p.Asn36Ser. This variant was previously described in one individual who presented with suspected neurofibromatosis type 2 (Wallace et al. 2004. PubMed ID: 15684865) and in a patient with a mild form of vestibular schwannomas (Heineman et al. 2015. PubMed ID: 25931164). However, this variant has also been reported in a cohort of presumably healthy individuals (Table S1 - Bodian et al. 2014. PubMed ID: 24728327). This variant is reported in 0.016% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-30000094-A-G) and has conflicting interpretations regarding its pathogenicity in ClinVar, ranging from benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/134892/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29618661, 32150022, 23975423, 25931164, 25925381, 16983642, 15684865, 24728327)
Comment:
The NF2 c.107A>G (p.Asn36Ser) missense change has a maximum subpopulation frequency of 0.029% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. This variant has been reported in an individual with a vestibular schwannoma (PMID: 15684865). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| In Silico Analysis of NF2 Gene Missense Mutations in Neurofibromatosis Type 2: From Genotype to Phenotype. | Heineman TE | Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology | 2015 | PMID: 25931164 |
| Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
| Mutation scanning of the NF2 gene: an improved service based on meta-PCR/sequencing, dosage analysis, and loss of heterozygosity analysis. | Wallace AJ | Genetic testing | 2004 | PMID: 15684865 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=NF2 | - | - | - | - |
Text-mined citations for rs372279458 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.