10-117547867-G-C

Variant names:

• chr10-117547867-G-C
• rs740734
• NM_004098.4:c.592-198G>C

Variant summary

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

The NM_004098.4(EMX2):​c.592-198G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,048 control chromosomes in the GnomAD database, including 3,562 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 0.21 (3562 hom., cov: 32)
• Consequence: EMX2 NM_004098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004098.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	NM_004098.4	MANE Select	c.592-198G>C		intron	N/A	NP_004089.1
	EMX2	NM_001165924.2		c.407-198G>C		intron	N/A	NP_001159396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	ENST00000553456.5	TSL:1 MANE Select	c.592-198G>C		intron	N/A	ENSP00000450962.3
	EMX2	ENST00000546446.2	TSL:1	n.551-198G>C		intron	N/A
	EMX2	ENST00000442245.5	TSL:2	c.407-198G>C		intron	N/A	ENSP00000474874.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31605 AN: 151932 Hom.: 3557 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.208 AC: 31630 AN: 152048 Hom.: 3562 Cov.: 32 AF XY: 0.213 AC XY: 15823 AN XY: 74330

African (AFR) AF: 0.154 AC: 6378 AN: 41470

American (AMR) AF: 0.223 AC: 3410 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3472

East Asian (EAS) AF: 0.188 AC: 965 AN: 5128

South Asian (SAS) AF: 0.388 AC: 1867 AN: 4818

European-Finnish (FIN) AF: 0.233 AC: 2463 AN: 10592

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14884 AN: 67966

Other (OTH) AF: 0.183 AC: 385 AN: 2108

Alfa AF: 0.199 Hom.: 403

Bravo AF: 0.198

Asia WGS AF: 0.283 AC: 984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.52
PhyloP100		-0.47
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: rs740734; hg19: chr10-119307378;