dbSNP rs1805190: EIF2AK3:p.Leu18_Leu21del (chr2-88627211-CCAGCAGCAGCAG-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004836.7(EIF2AK3):c.52_63delCTGCTGCTGCTG(p.Leu18_Leu21del) variant causes a conservative 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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
NM_004836.7 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Wolcott-Rallison syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp, G2P

EIF2AK3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2AK3	NM_004836.7 link	c.52_63delCTGCTGCTGCTG	p.Leu18_Leu21del	conservative_inframe_deletion	Exon 1 of 17	ENST00000303236.9	NP_004827.4	Q9NZJ5B3KY45
EIF2AK3	XM_047446430.1 link	c.52_63delCTGCTGCTGCTG	p.Leu18_Leu21del	conservative_inframe_deletion	Exon 1 of 12		XP_047302386.1
EIF2AK3	XM_047446428.1 link	c.17+466_17+477delCTGCTGCTGCTG		intron_variant	Intron 1 of 16		XP_047302384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EIF2AK3	ENST00000303236.9 link	c.52_63delCTGCTGCTGCTG	p.Leu18_Leu21del	conservative_inframe_deletion	Exon 1 of 17	1	NM_004836.7	ENSP00000307235.3	Q9NZJ5
EIF2AK3	ENST00000652099.1 link	n.49_60delCTGCTGCTGCTG		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000498211.1	A0A494BZR8
EIF2AK3	ENST00000652423.1 link	n.52_63delCTGCTGCTGCTG		non_coding_transcript_exon_variant	Exon 1 of 4			ENSP00000498948.1	A0A494C186
EIF2AK3	ENST00000682892.1 link	c.-145-13370_-145-13359delCTGCTGCTGCTG		intron_variant	Intron 2 of 17			ENSP00000507214.1	A0A804HIT4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000153

AC:

AN:

65220

AF XY:

0.0000268

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 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

African (AFR)

AF:

0.00

AC:

AN:

25618

American (AMR)

AF:

0.00

AC:

AN:

25616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22646

East Asian (EAS)

AF:

0.00

AC:

AN:

27398

South Asian (SAS)

AF:

0.0000284

AC:

AN:

70544

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3816

European-Non Finnish (NFE)

AF:

0.00000392

AC:

AN:

1019334

Other (OTH)

AF:

0.00

AC:

AN:

52996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.7

Splicing

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

Publications

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rs1805190

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over