ClinVar Genomic variation as it relates to human health
NM_000268.4(NF2):c.1564_1567del (p.Glu522fs)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000268.4(NF2):c.1564_1567del (p.Glu522fs)
Variation ID: 2138434 Accession: VCV002138434.2
- Type and length
-
Deletion, 4 bp
- Location
-
Cytogenetic: 22q12.2 22: 29678312-29678315 (GRCh38) [ NCBI UCSC ] 22: 30074301-30074304 (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 Feb 8, 2023 Feb 14, 2024 Mar 21, 2022 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000268.4:c.1564_1567del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000259.1:p.Glu522fs frameshift NM_001407053.1:c.1450_1453delGAGA NP_001393982.1:p.Glu484Lysfs frameshift NM_001407054.1:c.1441_1444delGAGA NP_001393983.1:p.Glu481Lysfs frameshift NM_001407055.1:c.1438_1441delGAGA NP_001393984.1:p.Glu480Lysfs frameshift NM_001407056.1:c.1450_1453delGAGA NP_001393985.1:p.Glu484Lysfs frameshift NM_001407057.1:c.1429_1432delGAGA NP_001393986.1:p.Glu477Lysfs frameshift NM_001407058.1:c.1441_1444delGAGA NP_001393987.1:p.Glu481Lysfs frameshift NM_001407059.1:c.1429_1432delGAGA NP_001393988.1:p.Glu477Lysfs frameshift NM_001407060.1:c.1564_1567delGAGA NP_001393989.1:p.Glu522Lysfs frameshift NM_001407062.1:c.1306_1309delGAGA NP_001393991.1:p.Glu436Lysfs frameshift NM_001407063.1:c.1315_1318delGAGA NP_001393992.1:p.Glu439Lysfs frameshift NM_001407064.1:c.1315_1318delGAGA NP_001393993.1:p.Glu439Lysfs frameshift NM_001407065.1:c.1030_1033delGAGA NP_001393994.1:p.Glu344Lysfs frameshift NM_001407066.1:c.1564_1567delGAGA NP_001393995.1:p.Glu522Lysfs frameshift NM_001407067.1:c.1333_1336delGAGA NP_001393996.1:p.Glu445Lysfs frameshift NM_016418.5:c.1564_1567del NP_057502.2:p.Glu522fs frameshift NM_181825.3:c.1564_1567del NP_861546.1:p.Glu522fs frameshift NM_181828.3:c.1438_1441del NP_861966.1:p.Glu480fs frameshift NM_181829.3:c.1441_1444del NP_861967.1:p.Glu481fs frameshift NM_181830.3:c.1315_1318del NP_861968.1:p.Glu439fs frameshift NM_181831.3:c.1315_1318del NP_861969.1:p.Glu439fs frameshift NM_181832.3:c.1564_1567del NP_861970.1:p.Glu522fs frameshift NM_181833.3:c.448-16439_448-16436del intron variant NR_156186.2:n.2046_2049del non-coding transcript variant NR_176267.1:n.1112_1115delGAGA NC_000022.11:g.29678313_29678316del NC_000022.10:g.30074302_30074305del NG_009057.1:g.79758_79761del LRG_511:g.79758_79761del LRG_511t1:c.1564_1567del LRG_511p1:p.Glu522Lysfs LRG_511t2:c.1564_1567del LRG_511p2:p.Glu522fs - Protein change
- E439fs, E481fs, E480fs, E522fs
- Other names
- -
- Canonical SPDI
- NC_000022.11:29678311:AGAGA:A
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
- 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 |
1972 | 2018 |
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. |
---|---|---|---|---|
Pathogenic (1) |
criteria provided, single submitter
|
Mar 21, 2022 | RCV003064650.2 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(Mar 21, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Neurofibromatosis, type 2
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV003444533.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with NF2-related conditions. … (more)
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with NF2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu522Lysfs*27) in the NF2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF2 are known to be pathogenic (PMID: 9643284, 16983642). (less)
|
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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Mutational spectrum of the NF2 gene: a meta-analysis of 12 years of research and diagnostic laboratory findings. | Ahronowitz I | Human mutation | 2007 | PMID: 16983642 |
Genotype/phenotype correlations in type 2 neurofibromatosis (NF2): evidence for more severe disease associated with truncating mutations. | Evans DG | Journal of medical genetics | 1998 | PMID: 9643284 |
Text-mined citations for this variant ...
HelpRecord last updated Feb 14, 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.