10-117543426-GGCCGCC-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 193270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-117543426-GGCCGCC-G is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 181 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMX2	NM_004098.4	c.173_178delCCGCCG	p.Ala58_Ala59del	disruptive_inframe_deletion	Exon 1 of 3	ENST00000553456.5	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_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMX2	ENST00000553456.5	c.173_178delCCGCCG	p.Ala58_Ala59del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_004098.4	ENSP00000450962.3
EMX2OS	ENST00000551288.5	n.574+874_574+879delGGCGGC		intron_variant	Intron 2 of 3	1
EMX2	ENST00000442245.5	c.173_178delCCGCCG	p.Ala58_Ala59del	disruptive_inframe_deletion	Exon 1 of 2	2		ENSP00000474874.1
EMX2	ENST00000616794.1	c.-141_-136delGCCGCC		upstream_gene_variant		2		ENSP00000480271.1

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

GnomAD3 exomes AF: 0.00108 AC: 224 AN: 208116 Hom.: 2 AF XY: 0.00102 AC XY: 117 AN XY: 114474

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 SAS exome AF: 0.0000358

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

Gnomad4 AFR exome AF: 0.000363

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.0000388

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.0000237

Gnomad4 FIN exome AF: 0.000517

Gnomad4 NFE exome AF: 0.00251

Gnomad4 OTH exome AF: 0.00208

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

Gnomad4 AFR AF: 0.000362

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000284

Gnomad4 NFE AF: 0.00212

Gnomad4 OTH AF: 0.00142

Bravo AF: 0.00122

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jul 13, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 17, 2015

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

EMX2-related disorder Benign:1

Jul 03, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Schizencephaly Benign:1

Nov 13, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs756693906; hg19: chr10-119302937;