Variant 2-88627211-CCAGCAGCAGCAG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000303236.9(EIF2AK3):c.52_63del(p.Leu18_Leu21del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000469 in 1,278,918 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L18L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

EIF2AK3
ENST00000303236.9 inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EIF2AK3	NM_004836.7 linkuse as main transcript	c.52_63del	p.Leu18_Leu21del	inframe_deletion	1/17	ENST00000303236.9	NP_004827.4
EIF2AK3	XM_047446430.1 linkuse as main transcript	c.52_63del	p.Leu18_Leu21del	inframe_deletion	1/12		XP_047302386.1
EIF2AK3	XM_047446428.1 linkuse as main transcript	c.17+466_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.52_63del	p.Leu18_Leu21del	inframe_deletion	1/17	1	NM_004836.7	ENSP00000307235	P1
EIF2AK3	ENST00000682892.1 linkuse as main transcript	c.-145-13370_-145-13359del		intron_variant				ENSP00000507214
EIF2AK3	ENST00000652099.1 linkuse as main transcript	c.50_61del	p.Leu18_Leu21del	inframe_deletion, NMD_transcript_variant	1/18			ENSP00000498211
EIF2AK3	ENST00000652423.1 linkuse as main transcript	c.52_63del	p.Leu18_Leu21del	inframe_deletion, NMD_transcript_variant	1/4			ENSP00000498948

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000153

AC:

AN:

65220

Hom.:

AF XY:

0.0000268

AC XY:

AN XY:

37308

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000710

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000469

AC:

AN:

1278918

Hom.:

AF XY:

0.00000794

AC XY:

AN XY:

630064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000284

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000392

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over