rs2287350

chr2-37141309-T-C

Variant summary

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

The NM_001135651.3(EIF2AK2):c.389+244A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,082 control chromosomes in the GnomAD database, including 8,268 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 0.31 (8268 hom., cov: 32)
• Consequence: EIF2AK2 NM_001135651.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.837

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2AK2	NM_001135651.3	c.389+244A>G		intron_variant		ENST00000233057.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2AK2	ENST00000233057.9	c.389+244A>G		intron_variant		2	NM_001135651.3	P2

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46817 AN: 151964 Hom.: 8269 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.308 AC: 46823 AN: 152082 Hom.: 8268 Cov.: 32 AF XY: 0.310 AC XY: 23071 AN XY: 74326

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.342

Alfa AF: 0.381 Hom.: 19498

Bravo AF: 0.294

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.74
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

Other links and lift over

dbSNP: rs2287350; hg19: chr2-37368452;