NM_001427.4:c.686-1388A>G

Variant names:

• chr7-155460983-A-G
• rs2361688
• NM_001427.4:c.686-1388A>G

Variant summary

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

The NM_001427.4(EN2):​c.686-1388A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,060 control chromosomes in the GnomAD database, including 41,097 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 0.73 (41097 hom., cov: 32)
• Consequence: EN2 NM_001427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.704
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EN2	NM_001427.4	c.686-1388A>G		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.686-1388A>G		intron_variant	Intron 1 of 1	1	NM_001427.4	ENSP00000297375.4

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111431 AN: 151942 Hom.: 41038 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.736

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

GnomAD4 genome AF: 0.734 AC: 111551 AN: 152060 Hom.: 41097 Cov.: 32 AF XY: 0.732 AC XY: 54379 AN XY: 74312

African (AFR) AF: 0.750 AC: 31118 AN: 41510

American (AMR) AF: 0.784 AC: 11992 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2420 AN: 3468

East Asian (EAS) AF: 0.940 AC: 4841 AN: 5152

South Asian (SAS) AF: 0.694 AC: 3343 AN: 4820

European-Finnish (FIN) AF: 0.672 AC: 7115 AN: 10584

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48364 AN: 67920

Other (OTH) AF: 0.737 AC: 1556 AN: 2112

Alfa AF: 0.682 Hom.: 5049

Bravo AF: 0.746

Asia WGS AF: 0.806 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.59
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2361688; hg19: chr7-155253678;