rs4717034

Variant names:

• chr7-155462202-C-T
• rs4717034
• NM_001427.4:c.686-169C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001427.4(EN2):​c.686-169C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,250 control chromosomes in the GnomAD database, including 1,545 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 0.14 (1545 hom., cov: 33)
• Consequence: EN2 NM_001427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EN2	NM_001427.4	c.686-169C>T		intron_variant	Intron 1 of 1	ENST00000297375.4	NP_001418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EN2	ENST00000297375.4	c.686-169C>T		intron_variant	Intron 1 of 1	1	NM_001427.4	ENSP00000297375.4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20790 AN: 152132 Hom.: 1544 Cov.: 33

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20787 AN: 152250 Hom.: 1545 Cov.: 33 AF XY: 0.136 AC XY: 10155 AN XY: 74434

African (AFR) AF: 0.0643 AC: 2673 AN: 41554

American (AMR) AF: 0.147 AC: 2248 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3472

East Asian (EAS) AF: 0.191 AC: 988 AN: 5168

South Asian (SAS) AF: 0.111 AC: 537 AN: 4826

European-Finnish (FIN) AF: 0.152 AC: 1614 AN: 10600

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11596 AN: 68012

Other (OTH) AF: 0.151 AC: 318 AN: 2112

Alfa AF: 0.157 Hom.: 621

Bravo AF: 0.134

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.66
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4717034; hg19: chr7-155254897;