rs3808330

chr7-155463312-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001427.4(EN2):c.*625T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,546 control chromosomes in the GnomAD database, including 4,707 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 0.23 (4697 hom., cov: 32)
  • Exomes 𝑓: 0.15 (10 hom.)
• Consequence: EN2 NM_001427.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EN2	NM_001427.4	c.*625T>C		3_prime_UTR_variant	2/2	ENST00000297375.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EN2	ENST00000297375.4	c.*625T>C		3_prime_UTR_variant	2/2	1	NM_001427.4	P1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34390 AN: 151794 Hom.: 4682 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.152 AC: 96 AN: 632 Hom.: 10 Cov.: 0 AF XY: 0.136 AC XY: 61 AN XY: 450

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0500

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.227 AC: 34446 AN: 151914 Hom.: 4697 Cov.: 32 AF XY: 0.224 AC XY: 16655 AN XY: 74266

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.216

Alfa AF: 0.194 Hom.: 906

Bravo AF: 0.244

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.5
Dann	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs3808330; hg19: chr7-155256007;