10-117543426-GGCCGCCGCCGCC-GGCCGCC

Variant names:

• chr10-117543426-GGCCGCC-G
• rs756693906
• NM_004098.4:c.173_178delCCGCCG

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3 BP6_Very_Strong BS2

The NM_004098.4(EMX2):​c.173_178delCCGCCG​(p.Ala58_Ala59del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00198 in 1,597,702 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 29)
  • Exomes 𝑓: 0.0021 (10 hom.)
• Consequence: EMX2 NM_004098.4 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.70
• Publications: 0 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 -13 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_004098.4
• BP6: Variant 10-117543426-GGCCGCC-G is Benign according to our data. Variant chr10-117543426-GGCCGCC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 193270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 181 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	NM_004098.4	MANE Select	c.173_178delCCGCCG	p.Ala58_Ala59del	disruptive_inframe_deletion	Exon 1 of 3	NP_004089.1
	EMX2	NM_001165924.2		c.173_178delCCGCCG	p.Ala58_Ala59del	disruptive_inframe_deletion	Exon 1 of 2	NP_001159396.1
	EMX2OS	NR_002791.2		n.574+874_574+879delGGCGGC		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	ENST00000553456.5	TSL:1 MANE Select	c.173_178delCCGCCG	p.Ala58_Ala59del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000450962.3
	EMX2OS	ENST00000551288.5	TSL:1	n.574+874_574+879delGGCGGC		intron	N/A
	EMX2	ENST00000442245.5	TSL:2	c.173_178delCCGCCG	p.Ala58_Ala59del	disruptive_inframe_deletion	Exon 1 of 2	ENSP00000474874.1

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 181 AN: 151826 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00212

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00108 AC: 224 AN: 208116 AF XY: 0.00102

Gnomad AFR exome AF: 0.000826

Gnomad AMR exome AF: 0.00123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000642

Gnomad FIN exome AF: 0.000329

Gnomad NFE exome AF: 0.00176

Gnomad OTH exome AF: 0.00210

GnomAD4 exome AF: 0.00206 AC: 2985 AN: 1445770 Hom.: 10 AF XY: 0.00204 AC XY: 1466 AN XY: 717914

African (AFR) AF: 0.000363 AC: 12 AN: 33102

American (AMR) AF: 0.00116 AC: 50 AN: 43100

Ashkenazi Jewish (ASJ) AF: 0.0000388 AC: 1 AN: 25774

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38656

South Asian (SAS) AF: 0.0000237 AC: 2 AN: 84480

European-Finnish (FIN) AF: 0.000517 AC: 26 AN: 50254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00251 AC: 2769 AN: 1105016

Other (OTH) AF: 0.00208 AC: 124 AN: 59638

GnomAD4 genome AF: 0.00119 AC: 181 AN: 151932 Hom.: 1 Cov.: 29 AF XY: 0.00125 AC XY: 93 AN XY: 74268

African (AFR) AF: 0.000362 AC: 15 AN: 41418

American (AMR) AF: 0.00105 AC: 16 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00212 AC: 144 AN: 67940

Other (OTH) AF: 0.00142 AC: 3 AN: 2106

Alfa AF: 0.000510 Hom.: 0

Bravo AF: 0.00122

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	EMX2-related disorder (1)
-	-	1	Schizencephaly (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7
Mutation Taster		=186/14	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs756693906; hg19: chr10-119302937;