rs7794177

Variant names:

• chr7-155459924-C-G
• rs7794177
• NM_001427.4:c.685+862C>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.685+862C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 152,320 control chromosomes in the GnomAD database, including 432 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 0.069 (432 hom., cov: 33)
• Consequence: EN2 NM_001427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001427.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EN2	NM_001427.4	MANE Select	c.685+862C>G		intron	N/A	NP_001418.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EN2	ENST00000297375.4	TSL:1 MANE Select	c.685+862C>G		intron	N/A	ENSP00000297375.4

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10430 AN: 152202 Hom.: 432 Cov.: 33

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0552

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0627

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0686 AC: 10445 AN: 152320 Hom.: 432 Cov.: 33 AF XY: 0.0690 AC XY: 5137 AN XY: 74478

African (AFR) AF: 0.0586 AC: 2437 AN: 41576

American (AMR) AF: 0.0551 AC: 843 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.152 AC: 735 AN: 4828

European-Finnish (FIN) AF: 0.0627 AC: 665 AN: 10612

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0753 AC: 5123 AN: 68026

Other (OTH) AF: 0.0789 AC: 167 AN: 2116

Alfa AF: 0.0730 Hom.: 56

Bravo AF: 0.0639

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.55
PhyloP100		-0.068
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: rs7794177; hg19: chr7-155252619;