dbSNP rs3808330: EN2:c.*625T>C (chr7-155463312-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001427.4(EN2):c.*625T>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 0.226 in 152,546 control chromosomes in the GnomAD database, including 4,707 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 0.23 ( 4697 hom., cov: 32)

Exomes 𝑓: 0.15 ( 10 hom. )

Consequence

EN2
NM_001427.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.294

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

EN2 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EN2	NM_001427.4 link	c.*625T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000297375.4	NP_001418.2	P19622

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EN2	ENST00000297375.4 link	c.*625T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_001427.4	ENSP00000297375.4		P19622

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34390

AN:

151794

Hom.:

4682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.260

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.152

AC:

AN:

632

Hom.:

Cov.:

AF XY:

0.136

AC XY:

AN XY:

450

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0500

AC:

AN:

South Asian (SAS)

AF:

0.375

AC:

AN:

European-Finnish (FIN)

AF:

0.159

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.139

AC:

AN:

518

Other (OTH)

AF:

0.208

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

AF:

0.227

AC:

34446

AN:

151914

Hom.:

4697

Cov.:

AF XY:

0.224

AC XY:

16655

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.374

AC:

15475

AN:

41364

American (AMR)

AF:

0.259

AC:

3962

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

656

AN:

3468

East Asian (EAS)

AF:

0.107

AC:

551

AN:

5144

South Asian (SAS)

AF:

0.257

AC:

1239

AN:

4818

European-Finnish (FIN)

AF:

0.140

AC:

1483

AN:

10586

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.155

AC:

10502

AN:

67948

Other (OTH)

AF:

0.216

AC:

456

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1278

2556

3833

5111

6389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.195

Hom.:

1460

Bravo

AF:

0.244

Asia WGS

AF:

0.188

AC:

653

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.5

(source)

DANN

Benign

0.83

PhyloP100

-0.29

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over