rs28999108

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001427.4(EN2):​c.686-517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 152,276 control chromosomes in the GnomAD database, including 23 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 0.015 ( 23 hom., cov: 33)

Consequence

EN2
NM_001427.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.131
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.015 (2280/152276) while in subpopulation NFE AF= 0.0259 (1762/68008). AF 95% confidence interval is 0.0249. There are 23 homozygotes in gnomad4. There are 1003 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2280 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EN2NM_001427.4 linkuse as main transcriptc.686-517C>T intron_variant ENST00000297375.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EN2ENST00000297375.4 linkuse as main transcriptc.686-517C>T intron_variant 1 NM_001427.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0150
AC:
2278
AN:
152158
Hom.:
23
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00391
Gnomad AMI
AF:
0.0121
Gnomad AMR
AF:
0.00726
Gnomad ASJ
AF:
0.0107
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00352
Gnomad FIN
AF:
0.0144
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0259
Gnomad OTH
AF:
0.0115
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0150
AC:
2280
AN:
152276
Hom.:
23
Cov.:
33
AF XY:
0.0135
AC XY:
1003
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.00390
Gnomad4 AMR
AF:
0.00725
Gnomad4 ASJ
AF:
0.0107
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00394
Gnomad4 FIN
AF:
0.0144
Gnomad4 NFE
AF:
0.0259
Gnomad4 OTH
AF:
0.0113
Alfa
AF:
0.0181
Hom.:
2
Bravo
AF:
0.0144
Asia WGS
AF:
0.00346
AC:
12
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
3.4
DANN
Benign
0.60

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.

Other links and lift over

dbSNP: rs28999108; hg19: chr7-155254549; API