chr2-37149171-G-C

Variant names:

• chr2-37149171-G-C
• rs2307466
• NM_001135651.3:c.-183-148C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002759.4(EIF2AK2):​c.-331C>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0595 in 1,028,280 control chromosomes in the GnomAD database, including 2,119 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 0.047 (242 hom., cov: 32)
  • Exomes 𝑓: 0.062 (1877 hom.)
• Consequence: EIF2AK2 NM_002759.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96
• Publications: 14 publications found

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]

ARL14EPP1 (HGNC:54676): (ARL14EP pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002759.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2AK2	NM_001135651.3	MANE Select	c.-183-148C>G		intron	N/A	NP_001129123.1	P19525-1
	EIF2AK2	NM_002759.4		c.-331C>G		5_prime_UTR	Exon 2 of 17	NP_002750.1	P19525-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2AK2	ENST00000233057.9	TSL:2 MANE Select	c.-183-148C>G		intron	N/A	ENSP00000233057.4	P19525-1
	EIF2AK2	ENST00000395127.6	TSL:5	c.-331C>G		5_prime_UTR	Exon 2 of 17	ENSP00000378559.2	P19525-1
	EIF2AK2	ENST00000679507.1		c.-16-1349C>G		intron	N/A	ENSP00000506024.1	P19525-1

Frequencies

GnomAD3 genomes AF: 0.0468 AC: 7123 AN: 152130 Hom.: 238 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.0465

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.0941

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0629

Gnomad OTH AF: 0.0483

GnomAD4 exome AF: 0.0617 AC: 54055 AN: 876030 Hom.: 1877 Cov.: 13 AF XY: 0.0634 AC XY: 29178 AN XY: 460048

African (AFR) AF: 0.00977 AC: 217 AN: 22200

American (AMR) AF: 0.0799 AC: 3482 AN: 43596

Ashkenazi Jewish (ASJ) AF: 0.0480 AC: 1070 AN: 22278

East Asian (EAS) AF: 0.0121 AC: 449 AN: 36956

South Asian (SAS) AF: 0.103 AC: 7638 AN: 74310

European-Finnish (FIN) AF: 0.0479 AC: 2505 AN: 52340

Middle Eastern (MID) AF: 0.0718 AC: 328 AN: 4570

European-Non Finnish (NFE) AF: 0.0621 AC: 35981 AN: 579240

Other (OTH) AF: 0.0588 AC: 2385 AN: 40540

GnomAD4 genome AF: 0.0469 AC: 7137 AN: 152250 Hom.: 242 Cov.: 32 AF XY: 0.0476 AC XY: 3541 AN XY: 74442

African (AFR) AF: 0.0119 AC: 493 AN: 41554

American (AMR) AF: 0.0691 AC: 1057 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0465 AC: 161 AN: 3466

East Asian (EAS) AF: 0.0158 AC: 82 AN: 5178

South Asian (SAS) AF: 0.0946 AC: 456 AN: 4822

European-Finnish (FIN) AF: 0.0381 AC: 404 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0629 AC: 4276 AN: 68010

Other (OTH) AF: 0.0511 AC: 108 AN: 2114

Alfa AF: 0.0579 Hom.: 37

Bravo AF: 0.0460

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.75
PhyloP100		4.0
PromoterAI		0.020	Neutral
Mutation Taster		=298/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2307466; hg19: chr2-37376314;