ClinVar Genomic variation as it relates to human health
NM_001134407.3(GRIN2A):c.547T>A (p.Phe183Ile)
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.
Uncertain significance(5); Benign(1); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001134407.3(GRIN2A):c.547T>A (p.Phe183Ile)
Variation ID: 129189 Accession: VCV000129189.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.2 16: 9938419 (GRCh38) [ NCBI UCSC ] 16: 10032276 (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 May 17, 2014 May 1, 2024 Jan 28, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001134407.3:c.547T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001127879.1:p.Phe183Ile missense NM_000833.5:c.547T>A NP_000824.1:p.Phe183Ile missense NM_001134408.2:c.547T>A NP_001127880.1:p.Phe183Ile missense NC_000016.10:g.9938419A>T NC_000016.9:g.10032276A>T NG_011812.2:g.249336T>A Q12879:p.Phe183Ile - Protein change
- F183I
- Other names
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- Canonical SPDI
- NC_000016.10:9938418:A:T
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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
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00004
The Genome Aggregation Database (gnomAD) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00006
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 | ||
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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
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. |
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GRIN2A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2043 | 2094 |
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. |
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Likely benign (1) |
criteria provided, single submitter
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May 14, 2013 | RCV000117178.13 | |
Pathogenic (1) |
no assertion criteria provided
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Jan 1, 2017 | RCV000656052.9 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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May 10, 2023 | RCV000711852.21 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 28, 2024 | RCV000989528.18 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 27, 2017 | RCV002313887.9 |
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. |
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Uncertain significance
(Sep 18, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV000842258.1
First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018 |
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Uncertain significance
(Dec 10, 2020)
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criteria provided, single submitter
Method: clinical testing
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Landau-Kleffner syndrome
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003815185.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Likely benign
(May 14, 2013)
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criteria provided, single submitter
Method: clinical testing
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AllHighlyPenetrant
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000151342.1
First in ClinVar: May 17, 2014 Last updated: May 17, 2014 |
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Likely benign
(Apr 28, 2023)
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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: SCV001815411.2
First in ClinVar: Sep 08, 2021 Last updated: May 06, 2023 |
Comment:
See Variant Classification Assertion Criteria.
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Uncertain significance
(May 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
paternal
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV004026266.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
Comment:
PP3, PP4, PM2_SUP
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Likely benign
(Jan 28, 2024)
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criteria provided, single submitter
Method: clinical testing
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Landau-Kleffner syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001011206.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Landau-Kleffner syndrome
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001139948.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Uncertain significance
(Jan 01, 2023)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004141111.4
First in ClinVar: Nov 20, 2023 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Uncertain significance
(Oct 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000847626.5
First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024 |
Comment:
The p.F183I variant (also known as c.547T>A), located in coding exon 2 of the GRIN2A gene, results from a T to A substitution at nucleotide … (more)
The p.F183I variant (also known as c.547T>A), located in coding exon 2 of the GRIN2A gene, results from a T to A substitution at nucleotide position 547. The phenylalanine at codon 183 is replaced by isoleucine, an amino acid with highly similar properties. In one study, this variant was detected in an individual with benign epilepsy with centrotemporal spikes (rolandic epilepsy). The variant was not present in the patient's asymptomatic father (mother's variant status unknown) (Lemke JR et al. Nat. Genet., 2013 Sep;45:1067-72). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. (less)
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Pathogenic
(Jan 01, 2017)
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no assertion criteria provided
Method: case-control
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Childhood epilepsy with centrotemporal spikes
Affected status: yes
Allele origin:
germline
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Bioinformatics Core, Luxembourg Center for Systems Biomedicine
Study: EUROEPINOMICS COGIE
Accession: SCV000588328.1 First in ClinVar: Jun 01, 2018 Last updated: Jun 01, 2018 |
Comment:
CAADphred>15
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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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Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy. | Bobbili DR | European journal of human genetics : EJHG | 2018 | PMID: 29358611 |
Altered zinc sensitivity of NMDA receptors harboring clinically-relevant mutations. | Serraz B | Neuropharmacology | 2016 | PMID: 27288002 |
Experience with targeted next generation sequencing for the care of lung cancer: insights into promises and limitations of genomic oncology in day-to-day practice. | Rangachari D | Cancer treatment communications | 2015 | PMID: 26601054 |
Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases. | Yuan H | Molecular pharmacology | 2015 | PMID: 25904555 |
Rare variants in γ-aminobutyric acid type A receptor genes in rolandic epilepsy and related syndromes. | Reinthaler EM | Annals of neurology | 2015 | PMID: 25726841 |
Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. | Lemke JR | Nature genetics | 2013 | PMID: 23933819 |
Text-mined citations for rs587780353 ...
HelpRecord last updated May 08, 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.