Genetic Variant EN1:p.Ala207_Ala216del (chr2-118846520-TGCGGCCGCCGCCGCCGCCGCCACTGCCGCC-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2

The NM_001426.4(EN1):c.618_647delGGCGGCAGTGGCGGCGGCGGCGGCGGCCGC(p.Ala207_Ala216del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00226 in 1,288,790 control chromosomes in the GnomAD database, including 85 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 83 hom. )

Consequence

EN1
NM_001426.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.33

Variant links:

Genes affected

EN1 (HGNC:3342): (engrailed homeobox 1) 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]

EN1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001426.4.

BP6

Variant 2-118846520-TGCGGCCGCCGCCGCCGCCGCCACTGCCGCC-T is Benign according to our data. Variant chr2-118846520-TGCGGCCGCCGCCGCCGCCGCCACTGCCGCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3025150.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EN1	NM_001426.4 link	c.618_647delGGCGGCAGTGGCGGCGGCGGCGGCGGCCGC	p.Ala207_Ala216del	disruptive_inframe_deletion	Exon 1 of 2	ENST00000295206.7	NP_001417.3	Q05925

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EN1	ENST00000295206.7 link	c.618_647delGGCGGCAGTGGCGGCGGCGGCGGCGGCCGC	p.Ala207_Ala216del	disruptive_inframe_deletion	Exon 1 of 2	2	NM_001426.4	ENSP00000295206.5		Q05925

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

238

AN:

148858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00221

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000535

Gnomad ASJ

AF:

0.00850

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000528

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.00147

GnomAD3 exomes

AF:

0.00106

AC:

AN:

50024

Hom.:

AF XY:

0.000963

AC XY:

AN XY:

30108

show subpopulations

Gnomad AFR exome

AF:

0.00128

Gnomad AMR exome

AF:

0.000764

Gnomad ASJ exome

AF:

0.00213

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.000156

Gnomad NFE exome

AF:

0.00141

Gnomad OTH exome

AF:

0.00223

GnomAD4 exome

AF:

0.00234

AC:

2670

AN:

1139824

Hom.:

AF XY:

0.00235

AC XY:

1288

AN XY:

549030

show subpopulations

Gnomad4 AFR exome

AF:

0.00223

Gnomad4 AMR exome

AF:

0.000934

Gnomad4 ASJ exome

AF:

0.00831

Gnomad4 EAS exome

AF:

0.000379

Gnomad4 SAS exome

AF:

0.00271

Gnomad4 FIN exome

AF:

0.000825

Gnomad4 NFE exome

AF:

0.00234

Gnomad4 OTH exome

AF:

0.00249

GnomAD4 genome

AF:

0.00160

AC:

238

AN:

148966

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

112

AN XY:

72644

show subpopulations

Gnomad4 AFR

AF:

0.00221

Gnomad4 AMR

AF:

0.000534

Gnomad4 ASJ

AF:

0.00850

Gnomad4 EAS

AF:

0.000391

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000528

Gnomad4 NFE

AF:

0.00144

Gnomad4 OTH

AF:

0.00145

Alfa

AF:

0.00196

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EN1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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