2-206162090-C-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001959.4(EEF1B2):​c.383C>A​(p.Ser128*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

EEF1B2
NM_001959.4 stop_gained

Scores

5
1
1

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 6.87
Variant links:
Genes affected
EEF1B2 (HGNC:3208): (eukaryotic translation elongation factor 1 beta 2) This gene encodes a translation elongation factor. The protein is a guanine nucleotide exchange factor involved in the transfer of aminoacylated tRNAs to the ribosome. Alternative splicing results in three transcript variants which differ only in the 5' UTR. [provided by RefSeq, Jul 2008]
SNORA41 (HGNC:32634): (small nucleolar RNA, H/ACA box 41)
SNORD51 (HGNC:10201): (small nucleolar RNA, C/D box 51)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-206162090-C-A is Pathogenic according to our data. Variant chr2-206162090-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 689450.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EEF1B2NM_001959.4 linkc.383C>A p.Ser128* stop_gained Exon 4 of 6 ENST00000392222.7 NP_001950.1 P24534A0A024R3W7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EEF1B2ENST00000392222.7 linkc.383C>A p.Ser128* stop_gained Exon 4 of 6 1 NM_001959.4 ENSP00000376056.2 P24534

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Seizure;C2237142:Moderate global developmental delay;C3714756:Intellectual disability Pathogenic:1
Aug 05, 2019
Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement, Assistance Publique Hopitaux de Paris
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

A first LoF variant was reported in one family with autosomal recessive intellectual disabilities (Najmabadi et al, 2011). The NM_001959.3:c.383C>A, NP_001950.1:p.(Ser128*) variant segregates in the sibship, and is absent in general population alleles in gnomAD ascertained by July 2019. It is a LoF variant in a gene where another LoF variant has been supposed to induce similar symptoms. Moreover, there are multiple lines of computational evidence that support a deleterious effect on the gene or gene product. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.55
D
BayesDel_noAF
Pathogenic
0.55
CADD
Pathogenic
41
DANN
Uncertain
0.99
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.99
D
Vest4
0.41
GERP RS
4.4

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs1576016842; hg19: chr2-207026814; API