NM_001959.4:c.569A>G

Variant names:

• chr2-206162774-A-G
• NM_001959.4:c.569A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001959.4(EEF1B2):​c.569A>G​(p.Gln190Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar 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: 5.91
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39315695).

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.569A>G	p.Gln190Arg	missense	Exon 6 of 6	NP_001950.1	P24534
	EEF1B2	NM_001037663.2		c.569A>G	p.Gln190Arg	missense	Exon 7 of 7	NP_001032752.1	P24534
	EEF1B2	NM_021121.4		c.569A>G	p.Gln190Arg	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.569A>G	p.Gln190Arg	missense	Exon 6 of 6	ENSP00000376056.2	P24534
	EEF1B2	ENST00000236957.9	TSL:1	c.569A>G	p.Gln190Arg	missense	Exon 7 of 7	ENSP00000236957.5	P24534
	EEF1B2	ENST00000881937.1		c.653A>G	p.Gln218Arg	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	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.041
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.11
Sift	Benign	0.39	T
Sift4G	Benign	0.58	T
Polyphen		0.040	B
Vest4		0.50
MutPred		0.35		Gain of MoRF binding (P = 0.0533)
MVP		0.61
MPC		0.24
ClinPred		0.68	D
GERP RS		5.2
Varity_R		0.23
gMVP		0.65
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

hg19: chr2-207027498;