2-177231801-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006164.5(NFE2L2):c.802G>A(p.Val268Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,614,212 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 32 hom. )

Consequence

NFE2L2
NM_006164.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.963

Publications

13 publications found

Variant links:

Genes affected

NFE2L2 (HGNC:7782): (NFE2 like bZIP transcription factor 2) This gene encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. The encoded transcription factor regulates genes which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to injury and inflammation which includes the production of free radicals. Multiple transcript variants encoding different isoforms have been characterized for this gene. [provided by RefSeq, Sep 2015]

NFE2L2 Gene-Disease associations (from GenCC):

immunodeficiency, developmental delay, and hypohomocysteinemia
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P

NFE2L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005718589).

BP6

Variant 2-177231801-C-T is Benign according to our data. Variant chr2-177231801-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 134906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 382 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFE2L2	NM_006164.5 link	c.802G>A	p.Val268Met	missense_variant	Exon 5 of 5	ENST00000397062.8	NP_006155.2	Q16236-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFE2L2	ENST00000397062.8 link	c.802G>A	p.Val268Met	missense_variant	Exon 5 of 5	1	NM_006164.5	ENSP00000380252.3		Q16236-1

Frequencies

GnomAD3 genomes

AF:

0.00251

AC:

382

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00422

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00241

AC:

601

AN:

249402

AF XY:

0.00230

show subpopulations

Gnomad AFR exome

AF:

0.000581

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00473

Gnomad NFE exome

AF:

0.00385

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00430

AC:

6284

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

3020

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33480

American (AMR)

AF:

0.00123

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00461

AC:

246

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00517

AC:

5751

AN:

1112000

Other (OTH)

AF:

0.00354

AC:

214

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

389

778

1166

1555

1944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

228

456

684

912

1140

<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

AF:

0.00251

AC:

382

AN:

152330

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000601

AC:

AN:

41582

American (AMR)

AF:

0.00157

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00424

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00422

AC:

287

AN:

68030

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00355

Hom.:

Bravo

AF:

0.00260

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00422

AC:

ExAC

AF:

0.00240

AC:

290

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00398

EpiControl

AF:

0.00373

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NFE2L2: BP4, BS2 -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

NFE2L2-related disorder

Benign:1

Nov 05, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.13

.;T;.;.;T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.82

.;T;T;T;T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.0057

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L;.;.;.;.

PhyloP100

0.96

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.050

N;N;N;.;N;N

REVEL

Benign

0.088

Sift

Benign

0.18

T;T;T;.;T;T

Sift4G

Benign

0.31

T;T;T;T;.;T

Polyphen

0.0080

.;B;.;.;.;.

Vest4

0.085

MVP

0.35

MPC

0.17

ClinPred

0.0046

GERP RS

2.4

Varity_R

0.071

gMVP

0.21

Mutation Taster

=99/1

polymorphism

(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.

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