10-117543426-GGCC-G

Variant names:

• chr10-117543426-GGCC-G
• rs756693906
• NM_004098.4:c.176_178delCCG

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The ENST00000553456.5(EMX2):​c.176_178delCCG​(p.Ala59del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000205 in 1,597,242 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: EMX2 ENST00000553456.5 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000553456.5
• BP6: Variant 10-117543426-GGCC-G is Benign according to our data. Variant chr10-117543426-GGCC-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1711265.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 22 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000553456.5. 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.176_178delCCG	p.Ala59del	disruptive_inframe_deletion	Exon 1 of 3	NP_004089.1
	EMX2	NM_001165924.2		c.176_178delCCG	p.Ala59del	disruptive_inframe_deletion	Exon 1 of 2	NP_001159396.1
	EMX2OS	NR_002791.2		n.574+877_574+879delGGC		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	ENST00000553456.5	TSL:1 MANE Select	c.176_178delCCG	p.Ala59del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000450962.3
	EMX2OS	ENST00000551288.5	TSL:1	n.574+877_574+879delGGC		intron	N/A
	EMX2	ENST00000442245.5	TSL:2	c.176_178delCCG	p.Ala59del	disruptive_inframe_deletion	Exon 1 of 2	ENSP00000474874.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 151828 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.0000969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000298 AC: 62 AN: 208116 AF XY: 0.000314

Gnomad AFR exome AF: 0.000184

Gnomad AMR exome AF: 0.000189

Gnomad ASJ exome AF: 0.000109

Gnomad EAS exome AF: 0.000128

Gnomad FIN exome AF: 0.000110

Gnomad NFE exome AF: 0.000459

Gnomad OTH exome AF: 0.000764

GnomAD4 exome AF: 0.000211 AC: 305 AN: 1445308 Hom.: 0 AF XY: 0.000202 AC XY: 145 AN XY: 717672

African (AFR) AF: 0.0000605 AC: 2 AN: 33070

American (AMR) AF: 0.000232 AC: 10 AN: 43066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25758

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38630

South Asian (SAS) AF: 0.0000474 AC: 4 AN: 84450

European-Finnish (FIN) AF: 0.0000598 AC: 3 AN: 50154

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

European-Non Finnish (NFE) AF: 0.000253 AC: 279 AN: 1104810

Other (OTH) AF: 0.000101 AC: 6 AN: 59620

GnomAD4 genome AF: 0.000145 AC: 22 AN: 151934 Hom.: 0 Cov.: 29 AF XY: 0.000148 AC XY: 11 AN XY: 74268

African (AFR) AF: 0.0000966 AC: 4 AN: 41418

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 10580

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

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67944

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.000437 Hom.: 0

Bravo AF: 0.000132

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs756693906; hg19: chr10-119302937; COSMIC: COSV71294751; COSMIC: COSV71294751;