rs2307479

chr2-37135412-T-G

Variant summary

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

The NM_001135651.3(EIF2AK2):c.785+72A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 1,280,648 control chromosomes in the GnomAD database, including 1,243 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 0.057 (397 hom., cov: 32)
  • Exomes 𝑓: 0.034 (846 hom.)
• Consequence: EIF2AK2 NM_001135651.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2AK2	NM_001135651.3	c.785+72A>C		intron_variant		ENST00000233057.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2AK2	ENST00000233057.9	c.785+72A>C		intron_variant		2	NM_001135651.3	P2

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 8729 AN: 152134 Hom.: 394 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.0454

GnomAD4 exome AF: 0.0339 AC: 38205 AN: 1128396 Hom.: 846 AF XY: 0.0343 AC XY: 19583 AN XY: 571526

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0256

Gnomad4 ASJ exome AF: 0.0318

Gnomad4 EAS exome AF: 0.000509

Gnomad4 SAS exome AF: 0.0404

Gnomad4 FIN exome AF: 0.0244

Gnomad4 NFE exome AF: 0.0328

Gnomad4 OTH exome AF: 0.0364

GnomAD4 genome AF: 0.0575 AC: 8754 AN: 152252 Hom.: 397 Cov.: 32 AF XY: 0.0554 AC XY: 4124 AN XY: 74456

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0326

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0317

Gnomad4 FIN AF: 0.0253

Gnomad4 NFE AF: 0.0336

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.0402 Hom.: 53

Bravo AF: 0.0603

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.0
Dann	Benign	0.77

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: rs2307479; hg19: chr2-37362555;