chr2-88627211-C-CCAGCAGCAG

Position:

• chr2-88627211-C-CCAGCAGCAG

Variant summary

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

The ENST00000303236.9(EIF2AK3):​c.63_64insCTGCTGCTG​(p.Leu19_Leu21dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L21L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: EIF2AK3 ENST00000303236.9 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.853

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2AK3	NM_004836.7	c.63_64insCTGCTGCTG	p.Leu19_Leu21dup	inframe_insertion	1/17	ENST00000303236.9	NP_004827.4
EIF2AK3	XM_047446430.1	c.63_64insCTGCTGCTG	p.Leu19_Leu21dup	inframe_insertion	1/12		XP_047302386.1
EIF2AK3	XM_047446428.1	c.17+477_17+478insCTGCTGCTG		intron_variant			XP_047302384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2AK3	ENST00000303236.9	c.63_64insCTGCTGCTG	p.Leu19_Leu21dup	inframe_insertion	1/17	1	NM_004836.7	ENSP00000307235	P1
EIF2AK3	ENST00000682892.1	c.-145-13359_-145-13358insCTGCTGCTG		intron_variant				ENSP00000507214
EIF2AK3	ENST00000652099.1	c.61_62insCTGCTGCTG	p.Leu19_Leu21dup	inframe_insertion, NMD_transcript_variant	1/18			ENSP00000498211
EIF2AK3	ENST00000652423.1	c.63_64insCTGCTGCTG	p.Leu19_Leu21dup	inframe_insertion, NMD_transcript_variant	1/4			ENSP00000498948

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151044 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000469 AC: 6 AN: 1278938 Hom.: 0 Cov.: 0 AF XY: 0.00000635 AC XY: 4 AN XY: 630080

Gnomad4 AFR exome AF: 0.0000781

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000730

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000196

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151044 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73738

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1805190; hg19: chr2-88926729;