dbSNP rs3808329: EN2:c.*704A>G (chr7-155463391-A-G) – 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.*704A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,836 control chromosomes in the GnomAD database, including 4,695 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 ( 4675 hom., cov: 32)

Exomes 𝑓: 0.17 ( 20 hom. )

Consequence

EN2
NM_001427.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -7.78

Publications

1 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EN2	NM_001427.4 link	c.*704A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000297375.4	NP_001418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EN2	ENST00000297375.4 link	c.*704A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001427.4	ENSP00000297375.4

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34082

AN:

151598

Hom.:

4648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.0681

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.207

GnomAD4 exome

AF:

0.174

AC:

194

AN:

1118

Hom.:

Cov.:

AF XY:

0.187

AC XY:

143

AN XY:

764

show subpopulations

African (AFR)

AF:

0.344

AC:

AN:

American (AMR)

AF:

0.100

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

AN:

East Asian (EAS)

AF:

0.0652

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.0882

AC:

AN:

Middle Eastern (MID)

AF:

0.242

AC:

AN:

European-Non Finnish (NFE)

AF:

0.173

AC:

135

AN:

780

Other (OTH)

AF:

0.171

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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

AF:

0.225

AC:

34154

AN:

151718

Hom.:

4675

Cov.:

AF XY:

0.223

AC XY:

16536

AN XY:

74168

show subpopulations

African (AFR)

AF:

0.378

AC:

15593

AN:

41280

American (AMR)

AF:

0.232

AC:

3540

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

656

AN:

3466

East Asian (EAS)

AF:

0.114

AC:

584

AN:

5144

South Asian (SAS)

AF:

0.264

AC:

1265

AN:

4798

European-Finnish (FIN)

AF:

0.139

AC:

1469

AN:

10560

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.154

AC:

10489

AN:

67910

Other (OTH)

AF:

0.205

AC:

432

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1242

2485

3727

4970

6212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.0747

Hom.:

Bravo

AF:

0.238

Asia WGS

AF:

0.188

AC:

652

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.42

(source)

DANN

Benign

0.41

PhyloP100

-7.8

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

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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