rs200480185
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_001961.4(EEF2):c.811G>A(p.Gly271Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000182 in 1,614,006 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000099 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00019 ( 0 hom. )
Consequence
EEF2
NM_001961.4 missense
NM_001961.4 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 4.99
Genes affected
EEF2 (HGNC:3214): (eukaryotic translation elongation factor 2) This gene encodes a member of the GTP-binding translation elongation factor family. This protein is an essential factor for protein synthesis. It promotes the GTP-dependent translocation of the nascent protein chain from the A-site to the P-site of the ribosome. This protein is completely inactivated by EF-2 kinase phosporylation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, EEF2
BS2
?
High AC in GnomAd4 at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EEF2 | NM_001961.4 | c.811G>A | p.Gly271Ser | missense_variant | 6/15 | ENST00000309311.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EEF2 | ENST00000309311.7 | c.811G>A | p.Gly271Ser | missense_variant | 6/15 | 5 | NM_001961.4 | P1 | |
EEF2 | ENST00000598182.5 | n.88G>A | non_coding_transcript_exon_variant | 2/4 | 2 | ||||
EEF2 | ENST00000598436.1 | n.309G>A | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152206Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.0000836 AC: 21AN: 251192Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135808
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GnomAD4 exome AF: 0.000190 AC: 278AN: 1461800Hom.: 0 Cov.: 32 AF XY: 0.000182 AC XY: 132AN XY: 727204
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GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152206Hom.: 1 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74356
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | EEF2: PP2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 08, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 EEF2 protein function. ClinVar contains an entry for this variant (Variation ID: 447308). This variant has not been reported in the literature in individuals affected with EEF2-related conditions. This variant is present in population databases (rs200480185, gnomAD 0.02%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 271 of the EEF2 protein (p.Gly271Ser). - |
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 25, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 31, 2023 | The c.811G>A (p.G271S) alteration is located in exon 6 (coding exon 6) of the EEF2 gene. This alteration results from a G to A substitution at nucleotide position 811, causing the glycine (G) at amino acid position 271 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at