rs2240776

Variant names:

• chr10-117548013-T-A
• rs2240776
• NM_004098.4:c.592-52T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-117548013-T-A
• chr10-117548013-T-C
• chr10-117548013-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004098.4(EMX2):​c.592-52T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,566,696 control chromosomes in the GnomAD database, including 289,280 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 0.52 (22116 hom., cov: 30)
  • Exomes 𝑓: 0.61 (267164 hom.)
• Consequence: EMX2 NM_004098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619
• Publications: 13 publications found

Genes affected

EMX2 (HGNC:3341): (empty spiracles homeobox 2) This gene encodes a homeobox-containing transcription factor that is the homolog to the 'empty spiracles' gene in Drosophila. Research on this gene in humans has focused on its expression in three tissues: dorsal telencephalon, olfactory neuroepithelium, and urogenetial system. It is expressed in the dorsal telencephalon during development in a low rostral-lateral to high caudal-medial gradient and is proposed to pattern the neocortex into defined functional areas. It is also expressed in embryonic and adult olfactory neuroepithelia where it complexes with eukaryotic translation initiation factor 4E (eIF4E) and possibly regulates mRNA transport or translation. In the developing urogenital system, it is expressed in epithelial tissues and is negatively regulated by HOXA10. Alternative splicing results in multiple transcript variants encoding distinct proteins.[provided by RefSeq, Sep 2009]

EMX2 Gene-Disease associations (from GenCC):

• schizencephaly

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMX2	NM_004098.4	c.592-52T>A		intron_variant	Intron 2 of 2	ENST00000553456.5	NP_004089.1
EMX2	NM_001165924.2	c.407-52T>A		intron_variant	Intron 1 of 1		NP_001159396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMX2	ENST00000553456.5	c.592-52T>A		intron_variant	Intron 2 of 2	1	NM_004098.4	ENSP00000450962.3
EMX2	ENST00000546446.2	n.551-52T>A		intron_variant	Intron 2 of 2	1
EMX2	ENST00000442245.5	c.407-52T>A		intron_variant	Intron 1 of 1	2		ENSP00000474874.1
EMX2	ENST00000616794.1	c.107-52T>A		intron_variant	Intron 1 of 1	2		ENSP00000480271.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78803 AN: 151672 Hom.: 22110 Cov.: 30

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 0.610 AC: 862952 AN: 1414906 Hom.: 267164 Cov.: 34 AF XY: 0.607 AC XY: 424539 AN XY: 699608

African (AFR) AF: 0.290 AC: 9440 AN: 32508

American (AMR) AF: 0.581 AC: 21979 AN: 37854

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 13885 AN: 25362

East Asian (EAS) AF: 0.543 AC: 20407 AN: 37548

South Asian (SAS) AF: 0.461 AC: 37077 AN: 80450

European-Finnish (FIN) AF: 0.570 AC: 27070 AN: 47512

Middle Eastern (MID) AF: 0.587 AC: 3251 AN: 5542

European-Non Finnish (NFE) AF: 0.639 AC: 695512 AN: 1089216

Other (OTH) AF: 0.583 AC: 34331 AN: 58914

GnomAD4 genome AF: 0.519 AC: 78835 AN: 151790 Hom.: 22116 Cov.: 30 AF XY: 0.515 AC XY: 38236 AN XY: 74194

African (AFR) AF: 0.303 AC: 12521 AN: 41364

American (AMR) AF: 0.572 AC: 8728 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1916 AN: 3468

East Asian (EAS) AF: 0.560 AC: 2866 AN: 5114

South Asian (SAS) AF: 0.441 AC: 2118 AN: 4798

European-Finnish (FIN) AF: 0.561 AC: 5923 AN: 10552

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.630 AC: 42760 AN: 67926

Other (OTH) AF: 0.585 AC: 1231 AN: 2106

Alfa AF: 0.563 Hom.: 3063

Bravo AF: 0.519

Asia WGS AF: 0.445 AC: 1549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.80
DANN	Benign	0.51
PhyloP100		-0.62
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: rs2240776; hg19: chr10-119307524; COSMIC: COSV71294729; COSMIC: COSV71294729;