NM_001959.4:c.532G>C

Variant names:

• chr2-206162737-G-C
• rs201807235
• NM_001959.4:c.532G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001959.4(EEF1B2):​c.532G>C​(p.Val178Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V178I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EEF1B2 NM_001959.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62
• Publications: 0 publications found

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]

EEF1B2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001959.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1B2	NM_001959.4	MANE Select	c.532G>C	p.Val178Leu	missense	Exon 6 of 6	NP_001950.1	P24534
	EEF1B2	NM_001037663.2		c.532G>C	p.Val178Leu	missense	Exon 7 of 7	NP_001032752.1	P24534
	EEF1B2	NM_021121.4		c.532G>C	p.Val178Leu	missense	Exon 7 of 7	NP_066944.1	P24534

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1B2	ENST00000392222.7	TSL:1 MANE Select	c.532G>C	p.Val178Leu	missense	Exon 6 of 6	ENSP00000376056.2	P24534
	EEF1B2	ENST00000236957.9	TSL:1	c.532G>C	p.Val178Leu	missense	Exon 7 of 7	ENSP00000236957.5	P24534
	EEF1B2	ENST00000881937.1		c.616G>C	p.Val206Leu	missense	Exon 8 of 8	ENSP00000551996.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0038	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.28
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.054	T
Polyphen		0.0080	B
Vest4		0.34
MutPred		0.50		Loss of sheet (P = 0.1158)
MVP		0.56
MPC		0.23
ClinPred		0.95	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.52
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs201807235; hg19: chr2-207027461;