rs855768

Variant names:

• chr10-117547956-G-A
• rs855768
• NM_004098.4:c.592-109G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-117547956-G-A
• chr10-117547956-G-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.592-109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 1,473,990 control chromosomes in the GnomAD database, including 7,218 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 0.12 (1392 hom., cov: 31)
  • Exomes 𝑓: 0.083 (5826 hom.)
• Consequence: EMX2 NM_004098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMX2	NM_004098.4	c.592-109G>A		intron_variant	Intron 2 of 2	ENST00000553456.5	NP_004089.1
EMX2	NM_001165924.2	c.407-109G>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.592-109G>A		intron_variant	Intron 2 of 2	1	NM_004098.4	ENSP00000450962.3
EMX2	ENST00000546446.2	n.551-109G>A		intron_variant	Intron 2 of 2	1
EMX2	ENST00000442245.5	c.407-109G>A		intron_variant	Intron 1 of 1	2		ENSP00000474874.1
EMX2	ENST00000616794.1	c.107-109G>A		intron_variant	Intron 1 of 1	2		ENSP00000480271.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18275 AN: 151846 Hom.: 1390 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0619

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0734

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.0827 AC: 109337 AN: 1322026 Hom.: 5826 AF XY: 0.0818 AC XY: 53665 AN XY: 655938

African (AFR) AF: 0.202 AC: 6083 AN: 30076

American (AMR) AF: 0.130 AC: 4603 AN: 35450

Ashkenazi Jewish (ASJ) AF: 0.0646 AC: 1597 AN: 24718

East Asian (EAS) AF: 0.261 AC: 9213 AN: 35342

South Asian (SAS) AF: 0.0815 AC: 6290 AN: 77132

European-Finnish (FIN) AF: 0.136 AC: 5072 AN: 37160

Middle Eastern (MID) AF: 0.0774 AC: 325 AN: 4200

European-Non Finnish (NFE) AF: 0.0694 AC: 70924 AN: 1022366

Other (OTH) AF: 0.0941 AC: 5230 AN: 55582

GnomAD4 genome AF: 0.120 AC: 18285 AN: 151964 Hom.: 1392 Cov.: 31 AF XY: 0.122 AC XY: 9097 AN XY: 74278

African (AFR) AF: 0.201 AC: 8305 AN: 41408

American (AMR) AF: 0.109 AC: 1662 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0619 AC: 215 AN: 3472

East Asian (EAS) AF: 0.224 AC: 1148 AN: 5126

South Asian (SAS) AF: 0.0806 AC: 387 AN: 4800

European-Finnish (FIN) AF: 0.122 AC: 1295 AN: 10594

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0734 AC: 4991 AN: 67976

Other (OTH) AF: 0.116 AC: 244 AN: 2110

Alfa AF: 0.109 Hom.: 144

Bravo AF: 0.124

Asia WGS AF: 0.161 AC: 556 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	13
DANN	Benign	0.72
PhyloP100		0.24
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: rs855768; hg19: chr10-119307467;