rs3808331

Variant names:

• chr7-155462079-T-C
• rs3808331
• NM_001427.4:c.686-292T>C

Variant summary

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

The NM_001427.4(EN2):​c.686-292T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 152,242 control chromosomes in the GnomAD database, including 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 0.084 (591 hom., cov: 33)
• Consequence: EN2 NM_001427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EN2	NM_001427.4	c.686-292T>C		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.686-292T>C		intron_variant	Intron 1 of 1	1	NM_001427.4	ENSP00000297375.4

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12701 AN: 152124 Hom.: 588 Cov.: 33

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.0983

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.0740

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0836 AC: 12721 AN: 152242 Hom.: 591 Cov.: 33 AF XY: 0.0841 AC XY: 6260 AN XY: 74436

African (AFR) AF: 0.0958 AC: 3978 AN: 41532

American (AMR) AF: 0.145 AC: 2221 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3470

East Asian (EAS) AF: 0.0981 AC: 508 AN: 5176

South Asian (SAS) AF: 0.0738 AC: 356 AN: 4822

European-Finnish (FIN) AF: 0.0740 AC: 785 AN: 10612

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0659 AC: 4485 AN: 68012

Other (OTH) AF: 0.0767 AC: 162 AN: 2112

Alfa AF: 0.0764 Hom.: 721

Bravo AF: 0.0916

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.21
DANN	Benign	0.76
PhyloP100		-0.87
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: rs3808331; hg19: chr7-155254774;