14-75009191-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_014239.4(EIF2B2):c.*3G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,784 control chromosomes in the GnomAD database, including 260 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.

Frequency

Genomes: 𝑓 0.021 ( 60 hom., cov: 32)

Exomes 𝑓: 0.013 ( 200 hom. )

Consequence

EIF2B2
NM_014239.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.254

Publications

8 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: Genomics England PanelApp, Illumina
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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.021 (3201/152102) while in subpopulation AFR AF = 0.0461 (1910/41466). AF 95% confidence interval is 0.0443. There are 60 homozygotes in GnomAd4. There are 1527 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF2B2	NM_014239.4 link	c.*3G>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000266126.10	NP_055054.1	P49770Q53XC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2B2	ENST00000266126.10 link	c.*3G>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_014239.4	ENSP00000266126.5		P49770
EIF2B2	ENST00000556668.1 link	n.639G>C		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3193

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0460

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.0102

Gnomad SAS

AF:

0.0415

Gnomad FIN

AF:

0.00161

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.0182

GnomAD2 exomes

AF:

0.0150

AC:

3759

AN:

251416

AF XY:

0.0158

show subpopulations

Gnomad AFR exome

AF:

0.0435

Gnomad AMR exome

AF:

0.00818

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.0122

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.0130

AC:

19068

AN:

1461682

Hom.:

200

Cov.:

AF XY:

0.0137

AC XY:

9949

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.0477

AC:

1598

AN:

33474

American (AMR)

AF:

0.00841

AC:

376

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00436

AC:

114

AN:

26132

East Asian (EAS)

AF:

0.0101

AC:

402

AN:

39696

South Asian (SAS)

AF:

0.0365

AC:

3150

AN:

86222

European-Finnish (FIN)

AF:

0.00165

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.0251

AC:

145

AN:

5768

European-Non Finnish (NFE)

AF:

0.0110

AC:

12277

AN:

1111902

Other (OTH)

AF:

0.0152

AC:

918

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1106

2213

3319

4426

5532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0210

AC:

3201

AN:

152102

Hom.:

Cov.:

AF XY:

0.0205

AC XY:

1527

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0461

AC:

1910

AN:

41466

American (AMR)

AF:

0.0118

AC:

181

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3470

East Asian (EAS)

AF:

0.0102

AC:

AN:

5172

South Asian (SAS)

AF:

0.0415

AC:

200

AN:

4816

European-Finnish (FIN)

AF:

0.00161

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0111

AC:

758

AN:

68008

Other (OTH)

AF:

0.0180

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

153

306

460

613

766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00811

Hom.:

Bravo

AF:

0.0220

Asia WGS

AF:

0.0290

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 31, 2017

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lynch syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Vanishing white matter disease

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.39

(source)

DANN

Benign

0.53

PhyloP100

-0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

14-75009191-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over