2-27364513-G-C

Variant names:

• chr2-27364513-G-C
• NM_001034116.2:c.1459C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001034116.2(EIF2B4):​c.1459C>G​(p.Leu487Val) 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 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EIF2B4 NM_001034116.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.41

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]

GTF3C2-AS2 (HGNC:55699): (GTF3C2 antisense RNA 2)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2B4	NM_001034116.2	c.1459C>G	p.Leu487Val	missense_variant	Exon 13 of 13	ENST00000347454.9	NP_001029288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2B4	ENST00000347454.9	c.1459C>G	p.Leu487Val	missense_variant	Exon 13 of 13	1	NM_001034116.2	ENSP00000233552.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T;D;.;.;D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Uncertain	2.4	.;M;.;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	.;N;N;N;N
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0020	.;D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D;D
Polyphen		0.89, 1.0, 0.56	.;P;D;P;.
Vest4		0.79
MutPred		0.68		.;Loss of stability (P = 0.1283);.;.;.;
MVP		0.79
MPC		1.1
ClinPred		0.94	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.92
gMVP		0.63

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: chr2-27587380;