7-155461985-T-C

Variant names:

• chr7-155461985-T-C
• rs3808332
• NM_001427.4:c.686-386T>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.686-386T>C 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 152,048 control chromosomes in the GnomAD database, including 1,550 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 (1550 hom., cov: 33)
• Consequence: EN2 NM_001427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EN2	NM_001427.4	c.686-386T>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.686-386T>C		intron_variant	Intron 1 of 1	1	NM_001427.4	ENSP00000297375.4

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20831 AN: 151930 Hom.: 1549 Cov.: 33

Gnomad AFR AF: 0.0648

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.137 AC: 20828 AN: 152048 Hom.: 1550 Cov.: 33 AF XY: 0.137 AC XY: 10172 AN XY: 74332

African (AFR) AF: 0.0646 AC: 2681 AN: 41482

American (AMR) AF: 0.147 AC: 2247 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 661 AN: 3472

East Asian (EAS) AF: 0.193 AC: 993 AN: 5148

South Asian (SAS) AF: 0.111 AC: 535 AN: 4816

European-Finnish (FIN) AF: 0.153 AC: 1619 AN: 10586

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.171 AC: 11612 AN: 67946

Other (OTH) AF: 0.152 AC: 321 AN: 2116

Alfa AF: 0.136 Hom.: 579

Bravo AF: 0.135

Asia WGS AF: 0.132 AC: 459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		-0.073
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: rs3808332; hg19: chr7-155254680;