rs2307483

Positions:

• chr2-37138655-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135651.3(EIF2AK2):​c.517-70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 1,291,672 control chromosomes in the GnomAD database, including 5,237 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (988 hom., cov: 32)
  • Exomes 𝑓: 0.083 (4249 hom.)
• Consequence: EIF2AK2 NM_001135651.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2AK2	NM_001135651.3	c.517-70T>C		intron_variant		ENST00000233057.9	NP_001129123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2AK2	ENST00000233057.9	c.517-70T>C		intron_variant		2	NM_001135651.3	ENSP00000233057.4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15293 AN: 152146 Hom.: 983 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0891

Gnomad FIN AF: 0.0559

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0761

Gnomad OTH AF: 0.0963

GnomAD4 exome AF: 0.0825 AC: 94042 AN: 1139408 Hom.: 4249 AF XY: 0.0828 AC XY: 47911 AN XY: 578572

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.0505

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.000602

Gnomad4 SAS exome AF: 0.0990

Gnomad4 FIN exome AF: 0.0593

Gnomad4 NFE exome AF: 0.0828

Gnomad4 OTH exome AF: 0.0905

GnomAD4 genome AF: 0.101 AC: 15333 AN: 152264 Hom.: 988 Cov.: 32 AF XY: 0.0984 AC XY: 7324 AN XY: 74452

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.0649

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0896

Gnomad4 FIN AF: 0.0559

Gnomad4 NFE AF: 0.0761

Gnomad4 OTH AF: 0.0948

Alfa AF: 0.104 Hom.: 197

Bravo AF: 0.104

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.3
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs2307483; hg19: chr2-37365798;