rs2270414

Variant names:

• chr2-37148789-G-A
• rs2270414
• NM_001135651.3:c.-17+68C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-37148789-G-A
• chr2-37148789-G-C
• chr2-37148789-G-T

Variant summary

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

The ENST00000233057.9(EIF2AK2):​c.-17+68C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 817,614 control chromosomes in the GnomAD database, including 101,707 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 0.46 (16553 hom., cov: 31)
  • Exomes 𝑓: 0.50 (85154 hom.)
• Consequence: EIF2AK2 ENST00000233057.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000233057.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2AK2	NM_001135651.3	MANE Select	c.-17+68C>T		intron	N/A	NP_001129123.1
	EIF2AK2	NM_002759.4		c.-17+68C>T		intron	N/A	NP_002750.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2AK2	ENST00000233057.9	TSL:2 MANE Select	c.-17+68C>T		intron	N/A	ENSP00000233057.4
	ARL14EPP1	ENST00000412776.1	TSL:6	n.260G>A		non_coding_transcript_exon	Exon 1 of 1
	EIF2AK2	ENST00000395127.6	TSL:5	c.-17+68C>T		intron	N/A	ENSP00000378559.2

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69896 AN: 151850 Hom.: 16548 Cov.: 31

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.491

GnomAD4 exome AF: 0.496 AC: 330174 AN: 665646 Hom.: 85154 Cov.: 7 AF XY: 0.490 AC XY: 176081 AN XY: 359496

African (AFR) AF: 0.385 AC: 7001 AN: 18194

American (AMR) AF: 0.407 AC: 17377 AN: 42716

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 11155 AN: 20636

East Asian (EAS) AF: 0.801 AC: 28686 AN: 35804

South Asian (SAS) AF: 0.391 AC: 27300 AN: 69774

European-Finnish (FIN) AF: 0.530 AC: 27210 AN: 51370

Middle Eastern (MID) AF: 0.493 AC: 2027 AN: 4110

European-Non Finnish (NFE) AF: 0.495 AC: 192760 AN: 389404

Other (OTH) AF: 0.495 AC: 16658 AN: 33638

GnomAD4 genome AF: 0.460 AC: 69937 AN: 151968 Hom.: 16553 Cov.: 31 AF XY: 0.466 AC XY: 34600 AN XY: 74270

African (AFR) AF: 0.381 AC: 15774 AN: 41444

American (AMR) AF: 0.437 AC: 6672 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1924 AN: 3468

East Asian (EAS) AF: 0.764 AC: 3940 AN: 5156

South Asian (SAS) AF: 0.410 AC: 1978 AN: 4826

European-Finnish (FIN) AF: 0.547 AC: 5770 AN: 10540

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32353 AN: 67950

Other (OTH) AF: 0.493 AC: 1041 AN: 2110

Alfa AF: 0.469 Hom.: 3404

Bravo AF: 0.454

Asia WGS AF: 0.547 AC: 1902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.38
PhyloP100		1.7
PromoterAI		0.027	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2270414; hg19: chr2-37375932;