Variant rs2254958 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002759.4(EIF2AK2):c.-308C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.401 in 949,826 control chromosomes in the GnomAD database, including 83,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10875 hom., cov: 31)

Exomes 𝑓: 0.41 ( 72348 hom. )

Consequence

EIF2AK2
NM_002759.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.69

Variant links:

Genes affected

EIF2AK2 (HGNC:9437): (eukaryotic translation initiation factor 2 alpha kinase 2) The protein encoded by this gene is a serine/threonine protein kinase that is activated by autophosphorylation after binding to dsRNA. The activated form of the encoded protein can phosphorylate translation initiation factor EIF2S1, which in turn inhibits protein synthesis. This protein is also activated by manganese ions and heparin. The encoded protein plays an important role in the innate immune response against multiple DNA and RNA viruses. [provided by RefSeq, Jul 2021]

EIF2AK2 links:

ARL14EPP1 (HGNC:):

ARL14EPP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 2-37149148-G-A is Benign according to our data. Variant chr2-37149148-G-A is described in ClinVar as [Benign]. Clinvar id is 1315570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2AK2	NM_001135651.3 linkuse as main transcript	c.-183-125C>T		intron_variant		ENST00000233057.9	NP_001129123.1	P19525-1Q8IW76

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2AK2	ENST00000233057.9 linkuse as main transcript	c.-183-125C>T		intron_variant		2	NM_001135651.3	ENSP00000233057.4		P19525-1

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53211

AN:

151888

Hom.:

10876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.763

Gnomad SAS

AF:

0.313

Gnomad FIN

AF:

0.514

Gnomad MID

AF:

0.343

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.384

GnomAD4 exome

AF:

0.411

AC:

328051

AN:

797820

Hom.:

72348

Cov.:

AF XY:

0.406

AC XY:

171765

AN XY:

422772

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.356

Gnomad4 ASJ exome

AF:

0.430

Gnomad4 EAS exome

AF:

0.801

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.493

Gnomad4 NFE exome

AF:

0.407

Gnomad4 OTH exome

AF:

0.406

GnomAD4 genome

AF:

0.350

AC:

53215

AN:

152006

Hom.:

10875

Cov.:

AF XY:

0.359

AC XY:

26680

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.364

Gnomad4 ASJ

AF:

0.446

Gnomad4 EAS

AF:

0.764

Gnomad4 SAS

AF:

0.313

Gnomad4 FIN

AF:

0.514

Gnomad4 NFE

AF:

0.407

Gnomad4 OTH

AF:

0.388

Alfa

AF:

0.349

Hom.:

4154

Bravo

AF:

0.338

Asia WGS

AF:

0.500

AC:

1739

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.1

DANN

Benign

0.67

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over