Variant chr2-88627211-CCAGCAG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP6BS1

The NM_004836.7(EIF2AK3):c.58_63del(p.Leu20_Leu21del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,289,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0024 ( 0 hom. )

Consequence

EIF2AK3
NM_004836.7 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.98

Variant links:

Genes affected

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 2-88627211-CCAGCAG-C is Benign according to our data. Variant chr2-88627211-CCAGCAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 3037443.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-88627211-CCAGCAG-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00239 (2718/1138122) while in subpopulation AMR AF= 0.0137 (290/21202). AF 95% confidence interval is 0.0124. There are 0 homozygotes in gnomad4_exome. There are 1497 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EIF2AK3	NM_004836.7 linkuse as main transcript	c.58_63del	p.Leu20_Leu21del	inframe_deletion	1/17	ENST00000303236.9	NP_004827.4
EIF2AK3	XM_047446430.1 linkuse as main transcript	c.58_63del	p.Leu20_Leu21del	inframe_deletion	1/12		XP_047302386.1
EIF2AK3	XM_047446428.1 linkuse as main transcript	c.17+472_17+477del		intron_variant			XP_047302384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
EIF2AK3	ENST00000303236.9 linkuse as main transcript	c.58_63del	p.Leu20_Leu21del	inframe_deletion	1/17	1	NM_004836.7	ENSP00000307235	P1
EIF2AK3	ENST00000682892.1 linkuse as main transcript	c.-145-13364_-145-13359del		intron_variant				ENSP00000507214
EIF2AK3	ENST00000652099.1 linkuse as main transcript	c.56_61del	p.Leu20_Leu21del	inframe_deletion, NMD_transcript_variant	1/18			ENSP00000498211
EIF2AK3	ENST00000652423.1 linkuse as main transcript	c.58_63del	p.Leu20_Leu21del	inframe_deletion, NMD_transcript_variant	1/4			ENSP00000498948

Frequencies

GnomAD3 genomes

AF:

0.0000464

AC:

AN:

150804

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000195

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000592

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00647

AC:

422

AN:

65220

Hom.:

AF XY:

0.00675

AC XY:

252

AN XY:

37308

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.00791

Gnomad ASJ exome

AF:

0.00326

Gnomad EAS exome

AF:

0.0138

Gnomad SAS exome

AF:

0.00525

Gnomad FIN exome

AF:

0.00751

Gnomad NFE exome

AF:

0.00628

Gnomad OTH exome

AF:

0.00315

GnomAD4 exome

AF:

0.00239

AC:

2718

AN:

1138122

Hom.:

AF XY:

0.00267

AC XY:

1497

AN XY:

559882

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.0137

Gnomad4 ASJ exome

AF:

0.00362

Gnomad4 EAS exome

AF:

0.00187

Gnomad4 SAS exome

AF:

0.00694

Gnomad4 FIN exome

AF:

0.00579

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.00267

GnomAD4 genome

AF:

0.0000464

AC:

AN:

150916

Hom.:

Cov.:

AF XY:

0.0000678

AC XY:

AN XY:

73726

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000195

Gnomad4 NFE

AF:

0.0000592

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EIF2AK3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 14, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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