7-155463391-A-G

Position:

• chr7-155463391-A-G

Variant summary

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

The NM_001427.4(EN2):​c.*704A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,836 control chromosomes in the GnomAD database, including 4,695 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 (4675 hom., cov: 32)
  • Exomes 𝑓: 0.17 (20 hom.)
• Consequence: EN2 NM_001427.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.78

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EN2	NM_001427.4	c.*704A>G		3_prime_UTR_variant	2/2	ENST00000297375.4	NP_001418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EN2	ENST00000297375.4	c.*704A>G		3_prime_UTR_variant	2/2	1	NM_001427.4	ENSP00000297375.4

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34082 AN: 151598 Hom.: 4648 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.174 AC: 194 AN: 1118 Hom.: 20 Cov.: 0 AF XY: 0.187 AC XY: 143 AN XY: 764

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.0652

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.0882

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.225 AC: 34154 AN: 151718 Hom.: 4675 Cov.: 32 AF XY: 0.223 AC XY: 16536 AN XY: 74168

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.205

Alfa AF: 0.0747 Hom.: 79

Bravo AF: 0.238

Asia WGS AF: 0.188 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.41

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: rs3808329; hg19: chr7-155256086;