rs1861972

Positions:

• chr7-155461298-G-A
• chr7-155461298-G-C
• chr7-155461298-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.686-1073G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,216 control chromosomes in the GnomAD database, including 40,444 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 (40444 hom., cov: 35)
• Consequence: EN2 NM_001427.4 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.40

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=-0.86).
• 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/exons	MANE	Protein	UniProt
EN2	NM_001427.4	c.686-1073G>A		intron_variant		ENST00000297375.4	NP_001418.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EN2	ENST00000297375.4	c.686-1073G>A		intron_variant		1	NM_001427.4	ENSP00000297375	P1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110569 AN: 152098 Hom.: 40386 Cov.: 35

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.672

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: 0.727 AC: 110688 AN: 152216 Hom.: 40444 Cov.: 35 AF XY: 0.725 AC XY: 53967 AN XY: 74406

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.731

Alfa AF: 0.681 Hom.: 5120

Bravo AF: 0.740

Asia WGS AF: 0.804 AC: 2793 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Autism, susceptibility to, 10 Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Nov 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.047
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs1861972; hg19: chr7-155253993;