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GeneBe

rs2307469

chr2-37109260-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.012 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 78 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EIF2AK2NM_001135651.3 linkuse as main transcriptc.1413C>G p.Leu471= synonymous_variant 15/17 ENST00000233057.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EIF2AK2ENST00000233057.9 linkuse as main transcriptc.1413C>G p.Leu471= synonymous_variant 15/172 NM_001135651.3 P2P19525-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0291
AC:
4436
AN:
152188
Hom.:
78
Cov.:
32
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.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0292
AC:
4447
AN:
152306
Hom.:
78
Cov.:
32
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.:
21
Bravo
AF:
0.0287
Asia WGS
AF:
0.0180
AC:
61
AN:
3478
EpiCase
AF:
0.0342
EpiControl
AF:
0.0316

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

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.

Other links and lift over

dbSNP: rs2307469; hg19: chr2-37336403; API