10-117544545-T-G

Variant names:

• chr10-117544545-T-G
• rs385209
• NM_004098.4:c.406+872T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004098.4(EMX2):​c.406+872T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 152,126 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00027 (0 hom., cov: 32)
• Consequence: EMX2 NM_004098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475
• Publications: 5 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]

EMX2OS (HGNC:18511): (EMX2 opposite strand/antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BS2: High AC in GnomAd4 at 41 AD,Unknown gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	NM_004098.4	MANE Select	c.406+872T>G		intron	N/A	NP_004089.1	Q04743-1
	EMX2	NM_001165924.2		c.406+872T>G		intron	N/A	NP_001159396.1	Q04743-2
	EMX2OS	NR_002791.2		n.503+21A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	ENST00000553456.5	TSL:1 MANE Select	c.406+872T>G		intron	N/A	ENSP00000450962.3	Q04743-1
	EMX2OS	ENST00000551288.5	TSL:1	n.503+21A>C		intron	N/A
	EMX2	ENST00000442245.5	TSL:2	c.406+872T>G		intron	N/A	ENSP00000474874.1	Q04743-2

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000870

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.000270 AC: 41 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74344

African (AFR) AF: 0.000892 AC: 37 AN: 41496

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 20844

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.3
DANN	Benign	0.37
PhyloP100		-0.47

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs385209;

hg19: chr10-119304056;