7-155461450-T-C

Variant names:

• chr7-155461450-T-C
• rs1861973
• NM_001427.4:c.686-921T>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.686-921T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,114 control chromosomes in the GnomAD database, including 40,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.73 (40464 hom., cov: 33)
• Consequence: EN2 NM_001427.4 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -2.19
• Publications: 26 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EN2	NM_001427.4	c.686-921T>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.686-921T>C		intron_variant	Intron 1 of 1	1	NM_001427.4	ENSP00000297375.4

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110564 AN: 151996 Hom.: 40406 Cov.: 33

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.731

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

GnomAD4 genome AF: 0.728 AC: 110683 AN: 152114 Hom.: 40464 Cov.: 33 AF XY: 0.726 AC XY: 53965 AN XY: 74342

African (AFR) AF: 0.731 AC: 30320 AN: 41488

American (AMR) AF: 0.782 AC: 11962 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2422 AN: 3470

East Asian (EAS) AF: 0.939 AC: 4836 AN: 5148

South Asian (SAS) AF: 0.692 AC: 3342 AN: 4830

European-Finnish (FIN) AF: 0.671 AC: 7113 AN: 10598

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48344 AN: 67972

Other (OTH) AF: 0.731 AC: 1544 AN: 2112

Alfa AF: 0.719 Hom.: 128321

Bravo AF: 0.740

Asia WGS AF: 0.806 AC: 2800 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Autism, susceptibility to, 10 Uncertain:1

Nov 01, 2005

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.58
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1861973; hg19: chr7-155254145;