2-206162737-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1B2	NM_001959.4	c.532G>C	p.Val178Leu	missense_variant	Exon 6 of 6	ENST00000392222.7	NP_001950.1
EEF1B2	NM_001037663.2	c.532G>C	p.Val178Leu	missense_variant	Exon 7 of 7		NP_001032752.1
EEF1B2	NM_021121.4	c.532G>C	p.Val178Leu	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.532G>C	p.Val178Leu	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

Jan 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.532G>C (p.V178L) alteration is located in exon 6 (coding exon 6) of the EEF1B2 gene. This alteration results from a G to C substitution at nucleotide position 532, causing the valine (V) at amino acid position 178 to be replaced by a leucine (L). 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	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;T;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;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.5	N;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.021	D;D;D
Sift4G	Uncertain	0.054	T;T;T
Polyphen		0.0080	B;B;B
Vest4		0.34
MutPred		0.50		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-207027461;