2-27369122-C-T

Variant names:

• chr2-27369122-C-T
• NM_001034116.2:c.302G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001034116.2(EIF2B4):​c.302G>A​(p.Arg101Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EIF2B4 NM_001034116.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.55

Genes affected

EIF2B4 (HGNC:3260): (eukaryotic translation initiation factor 2B subunit delta) Eukaryotic initiation factor 2B (EIF2B), which is necessary for protein synthesis, is a GTP exchange factor composed of five different subunits. The protein encoded by this gene is the fourth, or delta, subunit. Defects in this gene are a cause of leukoencephalopathy with vanishing white matter (VWM) and ovarioleukodystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [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=0.34809035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2B4	NM_001034116.2	c.302G>A	p.Arg101Gln	missense_variant	Exon 4 of 13	ENST00000347454.9	NP_001029288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2B4	ENST00000347454.9	c.302G>A	p.Arg101Gln	missense_variant	Exon 4 of 13	1	NM_001034116.2	ENSP00000233552.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.059	T;T;.;.;.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.35	T;T;T;T;T;T
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Uncertain	2.5	.;M;.;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.2	.;N;.;N;N;N
REVEL	Uncertain	0.47
Sift	Uncertain	0.0070	.;D;.;D;D;D
Sift4G	Uncertain	0.020	D;D;D;D;D;D
Polyphen		0.87, 0.92, 0.95	.;P;.;P;P;.
Vest4		0.38
MutPred		0.17		.;Loss of methylation at R101 (P = 0.0183);.;.;.;.;
MVP		0.81
MPC		1.1
ClinPred		0.96	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.16

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: chr2-27591989;