2-206162774-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1B2	NM_001959.4	c.569A>G	p.Gln190Arg	missense_variant	Exon 6 of 6	ENST00000392222.7	NP_001950.1
EEF1B2	NM_001037663.2	c.569A>G	p.Gln190Arg	missense_variant	Exon 7 of 7		NP_001032752.1
EEF1B2	NM_021121.4	c.569A>G	p.Gln190Arg	missense_variant	Exon 7 of 7		NP_066944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1B2	ENST00000392222.7	c.569A>G	p.Gln190Arg	missense_variant	Exon 6 of 6	1	NM_001959.4	ENSP00000376056.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Mar 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.569A>G (p.Q190R) alteration is located in exon 6 (coding exon 6) of the EEF1B2 gene. This alteration results from a A to G substitution at nucleotide position 569, causing the glutamine (Q) at amino acid position 190 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;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;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.86	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.040	B;B;B
Vest4		0.50
MutPred		0.35		Gain of MoRF binding (P = 0.0533);Gain of MoRF binding (P = 0.0533);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-207027498;