NM_001427.4:c.685+154G>C

Variant names:

• chr7-155459216-G-C
• rs3735652
• NM_001427.4:c.685+154G>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.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
• Publications: 0 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=-0.84).
• 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 rank	MANE	Protein	UniProt
EN2	NM_001427.4	c.685+154G>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.685+154G>C		intron_variant	Intron 1 of 1	1	NM_001427.4	ENSP00000297375.4

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

African (AFR) AF: 0.229 AC: 9511 AN: 41490

American (AMR) AF: 0.366 AC: 5592 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3466

East Asian (EAS) AF: 0.630 AC: 3242 AN: 5144

South Asian (SAS) AF: 0.322 AC: 1550 AN: 4820

European-Finnish (FIN) AF: 0.380 AC: 4028 AN: 10590

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26238 AN: 67928

Other (OTH) AF: 0.352 AC: 744 AN: 2112

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
PhyloP100		0.35
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: rs3735652; hg19: chr7-155251911; COSMIC: COSV52084213; COSMIC: COSV52084213;