rs2270414

Positions:

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

Variant summary

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

The NM_001135651.3(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 NM_001135651.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2AK2	NM_001135651.3	c.-17+68C>T		intron_variant		ENST00000233057.9	NP_001129123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2AK2	ENST00000233057.9	c.-17+68C>T		intron_variant		2	NM_001135651.3	ENSP00000233057	P2
ARL14EPP1	ENST00000412776.1	n.260G>A		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.541

Gnomad4 EAS exome AF: 0.801

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.495

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

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.493

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.38

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: rs2270414; hg19: chr2-37375932;