Genetic Variant NM_014239.4:c.38A>C (chr14-75003028-A-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_014239.4(EIF2B2):c.38A>C(p.Glu13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,836 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 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. E13G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 1 hom. )

Consequence

EIF2B2
NM_014239.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.88

Publications

0 publications found

Variant links:

Genes affected

EIF2B2 (HGNC:3258): (eukaryotic translation initiation factor 2B subunit beta) This gene encodes the beta subunit of eukaryotic initiation factor-2B (EIF2B). EIF2B is involved in protein synthesis and exchanges GDP and GTP for its activation and deactivation. [provided by RefSeq, Aug 2011]

EIF2B2 Gene-Disease associations (from GenCC):

leukoencephalopathy with vanishing white matter
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, Genomics England PanelApp
leukoencephalopathy with vanishing white matter 2
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
leukoencephalopathy with vanishing white matter
Inheritance: AR Classification: STRONG Submitted by: G2P
leukoencephalopathy with vanishing white matter 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
ovarioleukodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EIF2B2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26702493).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014239.4. 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
	EIF2B2	NM_014239.4	MANE Select	c.38A>C	p.Glu13Ala	missense	Exon 1 of 8	NP_055054.1	Q53XC2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF2B2	ENST00000266126.10	TSL:1 MANE Select	c.38A>C	p.Glu13Ala	missense	Exon 1 of 8	ENSP00000266126.5	P49770
EIF2B2	ENST00000932124.1		c.38A>C	p.Glu13Ala	missense	Exon 1 of 8	ENSP00000602183.1
EIF2B2	ENST00000932126.1		c.38A>C	p.Glu13Ala	missense	Exon 1 of 8	ENSP00000602185.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.066

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.11

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.9

PhyloP100

2.9

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.30

Sift

Benign

0.25

Sift4G

Benign

0.36

Polyphen

0.10

Vest4

0.40

MutPred

0.37

Gain of MoRF binding (P = 0.0273)

MVP

0.99

MPC

0.47

ClinPred

0.67

GERP RS

3.5

PromoterAI

-0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.36

gMVP

0.49

Mutation Taster

=33/67

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over