Variant 2-37109260-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001135651.3(EIF2AK2):c.1413C>G(p.Leu471=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,613,908 control chromosomes in the GnomAD database, including 844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 78 hom., cov: 32)

Exomes 𝑓: 0.031 ( 766 hom. )

Consequence

EIF2AK2
NM_001135651.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0120

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 2-37109260-G-C is Benign according to our data. Variant chr2-37109260-G-C is described in ClinVar as [Benign]. Clinvar id is 1571185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.012 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0292 (4447/152306) while in subpopulation NFE AF= 0.0323 (2196/68030). AF 95% confidence interval is 0.0312. There are 78 homozygotes in gnomad4. There are 2103 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 78 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2AK2	NM_001135651.3 linkuse as main transcript	c.1413C>G	p.Leu471=	synonymous_variant	15/17	ENST00000233057.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2AK2	ENST00000233057.9 linkuse as main transcript	c.1413C>G	p.Leu471=	synonymous_variant	15/17	2	NM_001135651.3	P2	P19525-1

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4436

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0288

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0352

Gnomad EAS

AF:

0.000960

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.0253

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.0320

GnomAD3 exomes

AF:

0.0287

AC:

7204

AN:

251330

Hom.:

122

AF XY:

0.0301

AC XY:

4096

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.0273

Gnomad AMR exome

AF:

0.0185

Gnomad ASJ exome

AF:

0.0387

Gnomad EAS exome

AF:

0.000870

Gnomad SAS exome

AF:

0.0409

Gnomad FIN exome

AF:

0.0242

Gnomad NFE exome

AF:

0.0327

Gnomad OTH exome

AF:

0.0368

GnomAD4 exome

AF:

0.0308

AC:

45044

AN:

1461602

Hom.:

766

Cov.:

AF XY:

0.0315

AC XY:

22904

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.0303

Gnomad4 AMR exome

AF:

0.0198

Gnomad4 ASJ exome

AF:

0.0389

Gnomad4 EAS exome

AF:

0.000580

Gnomad4 SAS exome

AF:

0.0404

Gnomad4 FIN exome

AF:

0.0241

Gnomad4 NFE exome

AF:

0.0317

Gnomad4 OTH exome

AF:

0.0306

GnomAD4 genome

AF:

0.0292

AC:

4447

AN:

152306

Hom.:

Cov.:

AF XY:

0.0282

AC XY:

2103

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0291

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.0352

Gnomad4 EAS

AF:

0.000963

Gnomad4 SAS

AF:

0.0317

Gnomad4 FIN

AF:

0.0253

Gnomad4 NFE

AF:

0.0323

Gnomad4 OTH

AF:

0.0312

Alfa

AF:

0.0325

Hom.:

Bravo

AF:

0.0287

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0342

EpiControl

AF:

0.0316

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
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

-0.45

CADD

Benign

5.2

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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