rs2254958

chr2-37149148-G-Achr2-37149148-G-Cchr2-37149148-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001135651.3(EIF2AK2):c.-183-125C>T variant causes a intron change. The variant allele was found at a frequency of 0.401 in 949,826 control chromosomes in the GnomAD database, including 83,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (10875 hom., cov: 31)
  • Exomes 𝑓: 0.41 (72348 hom.)
• Consequence: EIF2AK2 NM_001135651.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.69

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 2-37149148-G-A is Benign according to our data. Variant chr2-37149148-G-A is described in ClinVar as [Benign]. Clinvar id is 1315570.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
EIF2AK2	NM_001135651.3	c.-183-125C>T		intron_variant		ENST00000233057.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2AK2	ENST00000233057.9	c.-183-125C>T		intron_variant		2	NM_001135651.3	P2
ARL14EPP1	ENST00000412776.1	n.619G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53211 AN: 151888 Hom.: 10876 Cov.: 31

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.411 AC: 328051 AN: 797820 Hom.: 72348 Cov.: 11 AF XY: 0.406 AC XY: 171765 AN XY: 422772

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.356

Gnomad4 ASJ exome AF: 0.430

Gnomad4 EAS exome AF: 0.801

Gnomad4 SAS exome AF: 0.290

Gnomad4 FIN exome AF: 0.493

Gnomad4 NFE exome AF: 0.407

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.350 AC: 53215 AN: 152006 Hom.: 10875 Cov.: 31 AF XY: 0.359 AC XY: 26680 AN XY: 74320

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.388

Alfa AF: 0.349 Hom.: 4154

Bravo AF: 0.338

Asia WGS AF: 0.500 AC: 1739 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	8.1
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: rs2254958; hg19: chr2-37376291; COSMIC: COSV51795911; COSMIC: COSV51795911;