chr19-3982400-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001961.4(EEF2):​c.637G>A​(p.Gly213Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G213C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

EEF2
NM_001961.4 missense

Scores

5
4
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.86
Variant links:
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]
SNORD37 (HGNC:10166): (small nucleolar RNA, C/D box 37)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.807

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EEF2NM_001961.4 linkc.637G>A p.Gly213Ser missense_variant Exon 5 of 15 ENST00000309311.7 NP_001952.1 P13639
SNORD37NR_002602.1 linkn.*107G>A downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EEF2ENST00000309311.7 linkc.637G>A p.Gly213Ser missense_variant Exon 5 of 15 5 NM_001961.4 ENSP00000307940.5 P13639
EEF2ENST00000598436.1 linkn.135G>A non_coding_transcript_exon_variant Exon 1 of 4 2
EEF2ENST00000598182.5 linkn.-87G>A upstream_gene_variant 2
SNORD37ENST00000384048.1 linkn.*107G>A downstream_gene_variant 6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251208
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135828
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Uncertain
0.070
D
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Benign
0.023
T
MetaRNN
Pathogenic
0.81
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-0.080
N
REVEL
Benign
0.13
Sift
Benign
0.17
T
Sift4G
Benign
0.20
T
Polyphen
0.89
P
Vest4
0.84
MutPred
0.49
Loss of sheet (P = 0.0457);
MVP
0.67
ClinPred
0.81
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.25
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs773181804; hg19: chr19-3982398; API