7-155459499-G-T

Variant names:

• chr7-155459499-G-T
• rs6460013
• NM_001427.4:c.685+437G>T

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+437G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,176 control chromosomes in the GnomAD database, including 1,408 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 0.10 (1408 hom., cov: 33)
• Consequence: EN2 NM_001427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EN2	NM_001427.4	c.685+437G>T		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+437G>T		intron_variant	Intron 1 of 1	1	NM_001427.4	ENSP00000297375.4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15770 AN: 152058 Hom.: 1406 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.0542

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0455

Gnomad OTH AF: 0.0814

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

GnomAD4 genome AF: 0.104 AC: 15805 AN: 152176 Hom.: 1408 Cov.: 33 AF XY: 0.102 AC XY: 7581 AN XY: 74410

African (AFR) AF: 0.243 AC: 10085 AN: 41488

American (AMR) AF: 0.0687 AC: 1050 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3470

East Asian (EAS) AF: 0.0969 AC: 501 AN: 5168

South Asian (SAS) AF: 0.0420 AC: 203 AN: 4830

European-Finnish (FIN) AF: 0.0542 AC: 574 AN: 10600

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0455 AC: 3098 AN: 68024

Other (OTH) AF: 0.0810 AC: 171 AN: 2110

Alfa AF: 0.0515 Hom.: 228

Bravo AF: 0.112

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.83
PhyloP100		-2.5
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: rs6460013; hg19: chr7-155252194;