2-118846529-CGCCGCCGCCGCCACTGCCGCCGCG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3BP6BS1BS2

The NM_001426.4(EN1):​c.615_638delCGCGGCGGCAGTGGCGGCGGCGGC​(p.Ala206_Ala213del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,219,408 control chromosomes in the GnomAD database, including 35 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0080 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00077 ( 26 hom. )

Consequence

EN1
NM_001426.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.33
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_001426.4
BP6
Variant 2-118846529-CGCCGCCGCCGCCACTGCCGCCGCG-C is Benign according to our data. Variant chr2-118846529-CGCCGCCGCCGCCACTGCCGCCGCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 3050668.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00796 (1179/148122) while in subpopulation AFR AF= 0.0263 (1080/40992). AF 95% confidence interval is 0.025. There are 9 homozygotes in gnomad4. There are 553 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EN1NM_001426.4 linkc.615_638delCGCGGCGGCAGTGGCGGCGGCGGC p.Ala206_Ala213del 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
EN1ENST00000295206.7 linkc.615_638delCGCGGCGGCAGTGGCGGCGGCGGC p.Ala206_Ala213del disruptive_inframe_deletion Exon 1 of 2 2 NM_001426.4 ENSP00000295206.5 Q05925

Frequencies

GnomAD3 genomes
AF:
0.00798
AC:
1181
AN:
148014
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00469
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00323
Gnomad NFE
AF:
0.000166
Gnomad OTH
AF:
0.00737
GnomAD3 exomes
AF:
0.000480
AC:
9
AN:
18764
Hom.:
0
AF XY:
0.000253
AC XY:
3
AN XY:
11856
show subpopulations
Gnomad AFR exome
AF:
0.0260
Gnomad AMR exome
AF:
0.00236
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00185
GnomAD4 exome
AF:
0.000774
AC:
829
AN:
1071286
Hom.:
26
AF XY:
0.000688
AC XY:
352
AN XY:
511834
show subpopulations
Gnomad4 AFR exome
AF:
0.0277
Gnomad4 AMR exome
AF:
0.00273
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000127
Gnomad4 SAS exome
AF:
0.0000853
Gnomad4 FIN exome
AF:
0.0000814
Gnomad4 NFE exome
AF:
0.0000956
Gnomad4 OTH exome
AF:
0.00236
GnomAD4 genome
AF:
0.00796
AC:
1179
AN:
148122
Hom.:
9
Cov.:
32
AF XY:
0.00766
AC XY:
553
AN XY:
72206
show subpopulations
Gnomad4 AFR
AF:
0.0263
Gnomad4 AMR
AF:
0.00468
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000166
Gnomad4 OTH
AF:
0.00730
Alfa
AF:
0.00577
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

EN1-related disorder Benign:1
Jan 10, 2022
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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.

Other links and lift over

dbSNP: rs758084818; hg19: chr2-119604105; API