rs3824068

Variant names:

• chr7-155460803-C-T
• rs3824068
• NM_001427.4:c.686-1568C>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.686-1568C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,122 control chromosomes in the GnomAD database, including 9,591 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 0.34 (9591 hom., cov: 33)
• Consequence: EN2 NM_001427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EN2	NM_001427.4	MANE Select	c.686-1568C>T		intron	N/A	NP_001418.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EN2	ENST00000297375.4	TSL:1 MANE Select	c.686-1568C>T		intron	N/A	ENSP00000297375.4	P19622

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52328 AN: 152002 Hom.: 9581 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.344 AC: 52365 AN: 152122 Hom.: 9591 Cov.: 33 AF XY: 0.344 AC XY: 25602 AN XY: 74346

African (AFR) AF: 0.226 AC: 9383 AN: 41536

American (AMR) AF: 0.362 AC: 5537 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1122 AN: 3472

East Asian (EAS) AF: 0.637 AC: 3268 AN: 5134

South Asian (SAS) AF: 0.322 AC: 1550 AN: 4820

European-Finnish (FIN) AF: 0.378 AC: 4005 AN: 10584

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.386 AC: 26227 AN: 67980

Other (OTH) AF: 0.351 AC: 741 AN: 2110

Alfa AF: 0.360 Hom.: 1566

Bravo AF: 0.340

Asia WGS AF: 0.464 AC: 1612 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.35
DANN	Benign	0.40
PhyloP100		-2.1
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: rs3824068; hg19: chr7-155253498;