Variant chr7-155458738-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000297375.4(EN2):c.361C>T(p.Leu121Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,370,062 control chromosomes in the GnomAD database, including 164,063 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.41 ( 14234 hom., cov: 32)

Exomes 𝑓: 0.49 ( 149829 hom. )

Consequence

EN2
ENST00000297375.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

EN2 (HGNC:3343): (engrailed homeobox 2) Homeobox-containing genes are thought to have a role in controlling development. In Drosophila, the 'engrailed' (en) gene plays an important role during development in segmentation, where it is required for the formation of posterior compartments. Different mutations in the mouse homologs, En1 and En2, produced different developmental defects that frequently are lethal. The human engrailed homologs 1 and 2 encode homeodomain-containing proteins and have been implicated in the control of pattern formation during development of the central nervous system. [provided by RefSeq, Jul 2008]

EN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.9754937E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EN2	NM_001427.4 linkuse as main transcript	c.361C>T	p.Leu121Phe	missense_variant	1/2	ENST00000297375.4	NP_001418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EN2	ENST00000297375.4 linkuse as main transcript	c.361C>T	p.Leu121Phe	missense_variant	1/2	1	NM_001427.4	ENSP00000297375	P1

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

62151

AN:

151180

Hom.:

14230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.614

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.627

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.486

Gnomad MID

AF:

0.542

Gnomad NFE

AF:

0.498

Gnomad OTH

AF:

0.449

GnomAD3 exomes

AF:

0.541

AC:

1277

AN:

2360

Hom.:

344

AF XY:

0.534

AC XY:

706

AN XY:

1322

show subpopulations

Gnomad AFR exome

AF:

0.306

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.605

Gnomad EAS exome

AF:

0.732

Gnomad SAS exome

AF:

0.520

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.533

Gnomad OTH exome

AF:

0.522

GnomAD4 exome

AF:

0.493

AC:

600676

AN:

1218772

Hom.:

149829

Cov.:

AF XY:

0.494

AC XY:

292877

AN XY:

592734

show subpopulations

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.418

Gnomad4 ASJ exome

AF:

0.527

Gnomad4 EAS exome

AF:

0.626

Gnomad4 SAS exome

AF:

0.486

Gnomad4 FIN exome

AF:

0.474

Gnomad4 NFE exome

AF:

0.498

Gnomad4 OTH exome

AF:

0.483

GnomAD4 genome

AF:

0.411

AC:

62171

AN:

151290

Hom.:

14234

Cov.:

AF XY:

0.413

AC XY:

30515

AN XY:

73962

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.428

Gnomad4 ASJ

AF:

0.518

Gnomad4 EAS

AF:

0.627

Gnomad4 SAS

AF:

0.483

Gnomad4 FIN

AF:

0.486

Gnomad4 NFE

AF:

0.498

Gnomad4 OTH

AF:

0.451

Alfa

AF:

0.438

Hom.:

1905

Bravo

AF:

0.398

TwinsUK

AF:

0.506

AC:

1877

ALSPAC

AF:

0.513

AC:

1979

ExAC

AF:

0.242

AC:

1195

Asia WGS

AF:

0.511

AC:

1746

AN:

3418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.71

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0000020

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.2

REVEL

Benign

0.17

Sift

Benign

0.12

Sift4G

Benign

0.21

Polyphen

0.43

Vest4

0.038

MPC

2.0

ClinPred

0.0044

GERP RS

1.9

Varity_R

0.099

gMVP

0.089

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over