ClinVar Genomic variation as it relates to human health
NM_000268.4(NF2):c.517-1G>A
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
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NM_000268.4(NF2):c.517-1G>A
Variation ID: 423789 Accession: VCV000423789.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 22q12.2 22: 29655593 (GRCh38) [ NCBI UCSC ] 22: 30051582 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Apr 27, 2017 Feb 20, 2024 Jul 8, 2022 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- Other names
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- Canonical SPDI
- NC_000022.11:29655592:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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
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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. |
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NF2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1946 | 1992 |
Conditions - Germline
Condition
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Feb 21, 2017 | RCV000484883.1 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jul 8, 2022 | RCV001202383.11 |
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
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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
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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
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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. |
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Pathogenic
(Feb 21, 2017)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000573532.4
First in ClinVar: Apr 27, 2017 Last updated: Apr 27, 2017 |
Comment:
The c.517-1 G>A splice site variant in the NF2 gene has been previously observed in meningiomas and schwannomas (Goutagny et al., 2010; Piotrowski et al., … (more)
The c.517-1 G>A splice site variant in the NF2 gene has been previously observed in meningiomas and schwannomas (Goutagny et al., 2010; Piotrowski et al., 2014). This pathogenic variant destroys the canonical splice acceptor site in intron 5, and is expected to cause abnormal gene splicing. The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In summary, we consider this variant to be pathogenic. (less)
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Pathogenic
(Jun 18, 2020)
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criteria provided, single submitter
Method: clinical testing
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Neurofibromatosis, type 2
Affected status: yes
Allele origin:
maternal
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Baylor Genetics
Study: CSER-TexasKidsCanSeq
Accession: SCV001481184.2 First in ClinVar: Feb 28, 2021 Last updated: Feb 28, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
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Pathogenic
(Nov 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Neurofibromatosis, type 2
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002045421.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
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Pathogenic
(Jul 08, 2022)
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criteria provided, single submitter
Method: clinical testing
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Neurofibromatosis, type 2
(Somatic mutation)
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002761909.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
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Pathogenic
(Oct 15, 2019)
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criteria provided, single submitter
Method: clinical testing
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Neurofibromatosis, type 2
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001373493.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change affects an acceptor splice site in intron 5 of the NF2 gene. It is expected to disrupt RNA splicing and likely results … (more)
This sequence change affects an acceptor splice site in intron 5 of the NF2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with neurofibromatosis type 2 in a family (Invitae). ClinVar contains an entry for this variant (Variation ID: 423789). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NF2 are known to be pathogenic (PMID: 9643284, 16983642). For these reasons, this variant has been classified as Pathogenic. (less)
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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 |
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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 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
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 rs1064796632 ...
HelpRecord last updated Feb 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.