Variant 7-155458608-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001427.4(EN2):c.231C>G(p.Pro77Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00055 in 1,468,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00049 ( 0 hom. )

Consequence

EN2
NM_001427.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.616

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 7-155458608-C-G is Benign according to our data. Variant chr7-155458608-C-G is described in ClinVar as [Benign]. Clinvar id is 755379.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.616 with no splicing effect.

BS2

High AC in GnomAd4 at 162 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EN2	NM_001427.4 link	c.231C>G	p.Pro77Pro	synonymous_variant	1/2	ENST00000297375.4	NP_001418.2	P19622

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EN2	ENST00000297375.4 link	c.231C>G	p.Pro77Pro	synonymous_variant	1/2	1	NM_001427.4	ENSP00000297375.4		P19622

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

162

AN:

151722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000722

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00158

AC:

161

AN:

102010

Hom.:

AF XY:

0.00114

AC XY:

AN XY:

57768

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000685

Gnomad ASJ exome

AF:

0.000297

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00945

Gnomad NFE exome

AF:

0.000442

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.000491

AC:

646

AN:

1316672

Hom.:

Cov.:

AF XY:

0.000488

AC XY:

317

AN XY:

650236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000784

Gnomad4 ASJ exome

AF:

0.0000885

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000293

Gnomad4 FIN exome

AF:

0.00775

Gnomad4 NFE exome

AF:

0.000256

Gnomad4 OTH exome

AF:

0.000280

GnomAD4 genome

AF:

0.00107

AC:

162

AN:

151722

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.000722

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000678

Hom.:

Bravo

AF:

0.000329

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.8

DANN

Benign

0.68

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over