Variant chr15-39967713-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001013703.4(EIF2AK4):c.1387C>G(p.Arg463Gly) 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 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict 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

EIF2AK4
NM_001013703.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.07

Variant links:

Genes affected

EIF2AK4 (HGNC:19687): (eukaryotic translation initiation factor 2 alpha kinase 4) This gene encodes a member of a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 (EIF2), resulting in the downregulaton of protein synthesis. The encoded protein responds to amino acid deprivation by binding uncharged transfer RNAs. It may also be activated by glucose deprivation and viral infection. Mutations in this gene have been found in individuals suffering from autosomal recessive pulmonary venoocclusive-disease-2. [provided by RefSeq, Mar 2014]

EIF2AK4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), EIF2AK4. . Gene score misZ 2.6675 (greater than the threshold 3.09). Trascript score misZ 3.5194 (greater than threshold 3.09). GenCC has associacion of gene with pulmonary venoocclusive disease 2, pulmonary venoocclusive disease, heritable pulmonary arterial hypertension, pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2AK4	NM_001013703.4 linkuse as main transcript	c.1387C>G	p.Arg463Gly	missense_variant	9/39	ENST00000263791.10	NP_001013725.2	Q9P2K8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EIF2AK4	ENST00000263791.10 linkuse as main transcript	c.1387C>G	p.Arg463Gly	missense_variant	9/39	2	NM_001013703.4	ENSP00000263791.5	Q9P2K8-1
EIF2AK4	ENST00000559624.5 linkuse as main transcript	c.1387C>G	p.Arg463Gly	missense_variant	9/11	1		ENSP00000453148.1	Q9P2K8-3
EIF2AK4	ENST00000560855.5 linkuse as main transcript	c.802C>G	p.Arg268Gly	missense_variant	5/34	5		ENSP00000453575.1	H0YME5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249580

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135410

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.081

.;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.080

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.084

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.27

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.1

N;N

REVEL

Uncertain

0.39

Sift

Benign

0.31

T;T

Sift4G

Uncertain

0.019

D;T

Polyphen

0.14

B;P

Vest4

0.55

MutPred

0.65

Loss of stability (P = 0.1287);Loss of stability (P = 0.1287);

MVP

0.85

MPC

0.70

ClinPred

0.77

GERP RS

4.7

Varity_R

0.10

gMVP

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over