2-232557900-C-G

Variant names:

• chr2-232557900-C-G
• rs148255880
• NM_004846.4:c.152C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004846.4(EIF4E2):​c.152C>G​(p.Pro51Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,266 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P51L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: EIF4E2 NM_004846.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 1 publications found

Genes affected

EIF4E2 (HGNC:3293): (eukaryotic translation initiation factor 4E family member 2) Enables ubiquitin protein ligase binding activity. Involved in positive regulation of miRNA mediated inhibition of translation. Acts upstream of or within negative regulation of translation. Located in P-body. Part of mRNA cap binding activity complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E2	NM_004846.4	MANE Select	c.152C>G	p.Pro51Arg	missense	Exon 3 of 7	NP_004837.1	O60573-1
	EIF4E2	NM_001330202.2		c.137C>G	p.Pro46Arg	missense	Exon 3 of 7	NP_001317131.1
	EIF4E2	NM_001282958.2		c.152C>G	p.Pro51Arg	missense	Exon 3 of 8	NP_001269887.1	B8ZZ50

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E2	ENST00000258416.8	TSL:1 MANE Select	c.152C>G	p.Pro51Arg	missense	Exon 3 of 7	ENSP00000258416.3	O60573-1
	EIF4E2	ENST00000409098.5	TSL:1	c.152C>G	p.Pro51Arg	missense	Exon 3 of 7	ENSP00000386996.1	O60573-2
	EIF4E2	ENST00000931066.1		c.143C>G	p.Pro48Arg	missense	Exon 3 of 7	ENSP00000601125.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251224 AF XY: 0.00

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: 0.00000411 AC: 6 AN: 1461266 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726952

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5490

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111854

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.15
Sift	Uncertain	0.013	D
Sift4G	Benign	0.18	T
Polyphen		0.013	B
Vest4		0.52
MutPred		0.71		Gain of MoRF binding (P = 0.0019)
MVP		0.20
MPC		0.97
ClinPred		0.95	D
GERP RS		5.3
Varity_R		0.59
gMVP		0.31
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs148255880; hg19: chr2-233422610;