Genetic Variant EIF2AK3-DT:n.336_351dupGCGGATTCTGACTGTG (chr2-88627870-C-CGTGGCGGATTCTGACT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The XM_047446428.1(EIF2AK3):c.-181_-166dupAGTCAGAATCCGCCAC variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00556 in 151,904 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EIF2AK3
XM_047446428.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.71

Variant links:

Genes affected

EIF2AK3-DT (HGNC:54066): (EIF2AK3 divergent transcript)

EIF2AK3-DT links:

EIF2AK3 (HGNC:3255): (eukaryotic translation initiation factor 2 alpha kinase 3) The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]

EIF2AK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 2-88627870-C-CGTGGCGGATTCTGACT is Benign according to our data. Variant chr2-88627870-C-CGTGGCGGATTCTGACT is described in ClinVar as [Benign]. Clinvar id is 1335998.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00556 (844/151904) while in subpopulation AFR AF= 0.0198 (817/41280). AF 95% confidence interval is 0.0187. There are 11 homozygotes in gnomad4. There are 394 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2AK3	XM_047446428.1 link	c.-181_-166dupAGTCAGAATCCGCCAC		5_prime_UTR_variant	Exon 1 of 17		XP_047302384.1
EIF2AK3-DT	NR_135540.1 link	n.46_61dupGCGGATTCTGACTGTG		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
EIF2AK3-DT	ENST00000453008.3 link	n.336_351dupGCGGATTCTGACTGTG	non_coding_transcript_exon_variant	Exon 1 of 2	1
EIF2AK3	ENST00000682892.1 link	c.-145-14033_-145-14018dupAGTCAGAATCCGCCAC	intron_variant	Intron 2 of 17		ENSP00000507214.1	A0A804HIT4
EIF2AK3-DT	ENST00000688818.1 link	n.-9_7dupGCGGATTCTGACTGTG	non_coding_transcript_exon_variant	Exon 1 of 2
EIF2AK3-DT	ENST00000688818.1 link	n.-13_-12insGTGGCGGATTCTGACT	upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.00553

AC:

840

AN:

151786

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

272

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

208

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00556

AC:

844

AN:

151904

Hom.:

Cov.:

AF XY:

0.00531

AC XY:

394

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.0198

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00430

Hom.:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 16, 2019

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over