rs377237751

Variant names:

• chr15-39976797-GGAC-G
• NM_001013703.4:c.2211_2213delCGA

Your query was ambiguous. Multiple possible variants found:

• chr15-39976797-GGAC-G
• chr15-39976797-GGAC-GGACGAC
• chr15-39976797-GGAC-GGACGACGAC
• chr15-39976797-GGAC-GGACGACGACGAC
• chr15-39976797-GGAC-GGACGACGACGACGAC
• chr15-39976797-GGAC-GGACGACGACGACGACGAC

Variant summary

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

The NM_001013703.4(EIF2AK4):​c.2211_2213delCGA​(p.Asp737del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,094 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: EIF2AK4 NM_001013703.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.78

Genes affected

EIF2AK4 (HGNC:19687): (eukaryotic translation initiation factor 2 alpha kinase 4) This gene encodes a member of a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 (EIF2), resulting in the downregulaton of protein synthesis. The encoded protein responds to amino acid deprivation by binding uncharged transfer RNAs. It may also be activated by glucose deprivation and viral infection. Mutations in this gene have been found in individuals suffering from autosomal recessive pulmonary venoocclusive-disease-2. [provided by RefSeq, Mar 2014]

ACMG classification

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 rank	MANE	Protein	UniProt
EIF2AK4	NM_001013703.4	c.2211_2213delCGA	p.Asp737del	disruptive_inframe_deletion	Exon 12 of 39	ENST00000263791.10	NP_001013725.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2AK4	ENST00000263791.10	c.2211_2213delCGA	p.Asp737del	disruptive_inframe_deletion	Exon 12 of 39	2	NM_001013703.4	ENSP00000263791.5
EIF2AK4	ENST00000560855.5	c.1626_1628delCGA	p.Asp542del	disruptive_inframe_deletion	Exon 8 of 34	5		ENSP00000453575.1
EIF2AK4	ENST00000624709.1	n.-181_-179delGAC		upstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422094 Hom.: 0 AF XY: 0.00000142 AC XY: 1 AN XY: 705068

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000266

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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-40268998;