rs3735652

Positions:

• chr7-155459216-G-C
• chr7-155459216-G-T

Variant summary

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

The NM_001427.4(EN2):​c.685+154G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,034 control chromosomes in the GnomAD database, including 9,618 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 0.35 (9618 hom., cov: 33)
• Consequence: EN2 NM_001427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EN2	NM_001427.4	c.685+154G>C		intron_variant		ENST00000297375.4	NP_001418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EN2	ENST00000297375.4	c.685+154G>C		intron_variant		1	NM_001427.4	ENSP00000297375	P1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52528 AN: 151916 Hom.: 9613 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.346 AC: 52555 AN: 152034 Hom.: 9618 Cov.: 33 AF XY: 0.346 AC XY: 25707 AN XY: 74310

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.352

Alfa AF: 0.355 Hom.: 1228

Bravo AF: 0.342

Asia WGS AF: 0.459 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.43

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: rs3735652; hg19: chr7-155251911; COSMIC: COSV52084213; COSMIC: COSV52084213;