rs4717034

Positions:

• chr7-155462202-C-T

Variant summary

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

The NM_001427.4(EN2):​c.686-169C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,250 control chromosomes in the GnomAD database, including 1,545 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 0.14 (1545 hom., cov: 33)
• Consequence: EN2 NM_001427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EN2	NM_001427.4	c.686-169C>T		intron_variant		ENST00000297375.4	NP_001418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EN2	ENST00000297375.4	c.686-169C>T		intron_variant		1	NM_001427.4	ENSP00000297375.4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20790 AN: 152132 Hom.: 1544 Cov.: 33

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.137 AC: 20787 AN: 152250 Hom.: 1545 Cov.: 33 AF XY: 0.136 AC XY: 10155 AN XY: 74434

Gnomad4 AFR AF: 0.0643

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.151

Alfa AF: 0.157 Hom.: 308

Bravo AF: 0.134

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4717034; hg19: chr7-155254897;