ClinVar Genomic variation as it relates to human health
NM_001958.5(EEF1A2):c.364G>A (p.Glu122Lys)
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_001958.5(EEF1A2):c.364G>A (p.Glu122Lys)
Variation ID: 192252 Accession: VCV000192252.40
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 20q13.33 20: 63495062 (GRCh38) [ NCBI UCSC ] 20: 62126415 (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 Jun 8, 2015 May 12, 2024 Jan 19, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001958.5:c.364G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001949.1:p.Glu122Lys missense NC_000020.11:g.63495062C>T NC_000020.10:g.62126415C>T NG_034083.1:g.9254G>A Q05639:p.Glu122Lys - Protein change
- E122K
- Other names
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- Canonical SPDI
- NC_000020.11:63495061:C: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
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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
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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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EEF1A2 | No evidence available | No evidence available |
GRCh38 GRCh37 |
491 | 646 |
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 (2) |
criteria provided, single submitter
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Oct 4, 2018 | RCV000172840.7 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jan 19, 2024 | RCV000193799.15 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 28, 2017 | RCV000622866.5 | |
EEF1A2-related developmental and degenerative epileptic-dyskinetic encephalopathy
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Pathogenic (1) |
criteria provided, single submitter
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Feb 13, 2020 | RCV001030064.3 |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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May 1, 2021 | RCV001267946.22 |
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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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446465.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Microcephaly (present) , Intellectual disability (present) , Seizure (present) , Absent speech (present) , Global developmental delay (present) , Poor motor coordination (present) , Motor … (more)
Microcephaly (present) , Intellectual disability (present) , Seizure (present) , Absent speech (present) , Global developmental delay (present) , Poor motor coordination (present) , Motor stereotypies (present) , Sleep abnormality (present) , Short stature (present) (less)
Sex: male
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Pathogenic
(-)
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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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Laboratoire de Génétique Moléculaire, CHU Bordeaux
Accession: SCV001468930.1
First in ClinVar: Jan 17, 2021 Last updated: Jan 17, 2021 |
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Pathogenic
(Oct 04, 2018)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 38
Affected status: yes
Allele origin:
de novo
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Baylor Genetics
Accession: SCV001529140.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease causing [PMID 24697219, 26682508, … (more)
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease causing [PMID 24697219, 26682508, 27441201] (less)
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Pathogenic
(Oct 13, 2020)
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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: SCV001815518.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This … (more)
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32196822, 31477274, 27441201, 23033978, 23647072, 26740508, 19636410, 28911200, 28378778, 24697219, 3066688, 26682508) (less)
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Likely pathogenic
(Feb 18, 2015)
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criteria provided, single submitter
Method: clinical testing
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Epileptic encephalopathy, early infantile, 33
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000247256.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Pathogenic
(Oct 25, 2018)
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criteria provided, single submitter
Method: clinical testing
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Developmental and epileptic encephalopathy, 33
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Génétique des Maladies du Développement, Hospices Civils de Lyon
Accession: SCV001164200.1
First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020 |
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Pathogenic
(Feb 13, 2020)
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criteria provided, single submitter
Method: research
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EEF1A2-related developmental and degenerative epileptic-dyskinetic encephalopathy
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Epilepsy Neurogenetics Initiative, Children's Hospital of Philadelphia
Accession: SCV001192844.1
First in ClinVar: Apr 06, 2020 Last updated: Apr 06, 2020 |
Comment:
The EEF1A2 c.364G>A; p.Glu122Lys variant has been identified in three individuals with a developmental and epileptic encephalopathy characterized by global developmental delays, moderate to severe … (more)
The EEF1A2 c.364G>A; p.Glu122Lys variant has been identified in three individuals with a developmental and epileptic encephalopathy characterized by global developmental delays, moderate to severe intellectual disability, and intractable infantile or early childhood onset epilepsy. One individual had a hyperkinetic movement disorder characterized by choreoathetosis. The variant is confirmed de novo in two individuals; testing of both parents was not performed in the third individual. The variant is absent from population databases (ExAC, gnomAD) and is predicted to have a damaging effect on the protein by in silico models. Therefore, this variant has been classified as pathogenic. (less)
Clinical Features:
Absent speech (present) , Gait ataxia (present) , Inability to walk (present) , Intellectual disability, severe (present) , Focal seizures (present) , Generalized myoclonic seizures … (more)
Absent speech (present) , Gait ataxia (present) , Inability to walk (present) , Intellectual disability, severe (present) , Focal seizures (present) , Generalized myoclonic seizures (present) , Epileptic spasms (present) , Generalized tonic seizures (present) , Myoclonic atonic seizures (present) , Generalized tonic-clonic seizures (present) , Absence seizures (present) , Atypical absence seizures (present) , Hyperreflexia (present) , Choreoathetosis (present) , Autistic behavior (present) , Cortical visual impairment (present) (less)
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Pathogenic
(Feb 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV000742156.3
First in ClinVar: Apr 15, 2018 Last updated: Jan 07, 2023 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Global developmental delay (present) , Seizures (present) , Failure to thrive (present) , Gait disturbance (present) , Muscular hypotonia (present) , Hyperactive deep tendon reflexes … (more)
Global developmental delay (present) , Seizures (present) , Failure to thrive (present) , Gait disturbance (present) , Muscular hypotonia (present) , Hyperactive deep tendon reflexes (present) , Feeding difficulties (present) , Growth delay (present) (less)
Sex: male
Ethnicity/Population group: Hispanic
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Intellectual disability (present) , Global developmental delay (present) , Ventricular septal defect (present) , Seizures (present) , Failure to thrive (present) , Muscular hypotonia (present) … (more)
Intellectual disability (present) , Global developmental delay (present) , Ventricular septal defect (present) , Seizures (present) , Failure to thrive (present) , Muscular hypotonia (present) , Microcephaly (present) , Stereotypy (present) , Cortical visual impairment (present) , Feeding difficulties (present) , Dermatitis, atopic (present) , Hearing impairment (present) , Low-set ears (present) , Broad nasal tip (present) , Malar flattening (present) , Abnormality of the nose (present) , Self-injurious behavior (present) (less)
Sex: female
Ethnicity/Population group: Caucasian
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Pathogenic
(Mar 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Developmental and epileptic encephalopathy, 33
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV004045930.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Number of individuals with the variant: 1
Clinical Features:
Microcephaly (present) , Generalized-onset seizure (present) , EEG with generalized spikes (present) , Global developmental delay (present)
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Pathogenic
(Jan 19, 2024)
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criteria provided, single submitter
Method: clinical testing
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Developmental and epileptic encephalopathy, 33
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000774988.5
First in ClinVar: Oct 05, 2015 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 122 of the EEF1A2 protein … (more)
This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 122 of the EEF1A2 protein (p.Glu122Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurological disease, including epilepsy and intellectual disability (PMID: 24697219, 26682508, 27441201). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 192252). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EEF1A2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects EEF1A2 function (PMID: 3066688). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 01, 2021)
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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: SCV001746716.15
First in ClinVar: Jul 10, 2021 Last updated: May 12, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Apr 01, 2015)
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no assertion criteria provided
Method: literature only
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INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 38
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000223806.3
First in ClinVar: Jun 08, 2015 Last updated: Apr 08, 2022 |
Comment on evidence:
In a 12-year-old Japanese girl with autosomal dominant intellectual developmental disorder-38 (MRD38; 616393), Nakajima et al. (2015) identified a de novo heterozygous c.364G-A transition (c.364G-A, … (more)
In a 12-year-old Japanese girl with autosomal dominant intellectual developmental disorder-38 (MRD38; 616393), Nakajima et al. (2015) identified a de novo heterozygous c.364G-A transition (c.364G-A, NM_001958.3) in exon 4 of the EEF1A2 gene, resulting in a glu122-to-lys (E122K) substitution at a highly conserved residue in the fifth alpha-helix of domain I. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP (build 135/build 137) or Exome Sequencing Project (ESP6500) databases, or in 575 in-house control Japanese exomes. Domain I is involved in GTP/GDP binding, and the mutation may affect translational fidelity; however, functional studies of the variant were not performed. (less)
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Pathogenic
(Apr 26, 2018)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
de novo
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Department of Genetics, Robert DEBRE University Hospital
Accession: SCV004171547.1
First in ClinVar: Dec 02, 2023 Last updated: Dec 02, 2023 |
Clinical Features:
Intellectual disability (present)
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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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Novel de novo EEF1A2 missense mutations causing epilepsy and intellectual disability. | Lam WW | Molecular genetics & genomic medicine | 2016 | PMID: 27441201 |
Two cases of early-onset myoclonic seizures with continuous parietal delta activity caused by EEF1A2 mutations. | Inui T | Brain & development | 2016 | PMID: 26682508 |
De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability, autistic behaviors and epilepsy. | Nakajima J | Clinical genetics | 2015 | PMID: 24697219 |
Mutations in elongation factor EF-1 alpha affect the frequency of frameshifting and amino acid misincorporation in Saccharomyces cerevisiae. | Sandbaken MG | Genetics | 1988 | PMID: 3066688 |
Text-mined citations for this variant ...
HelpRecord last updated May 12, 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.