10-117543426-GGCC-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_004098.4(EMX2):c.176_178del(p.Ala59del) variant causes a 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 NM_004098.4 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_004098.4
• 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 id is 1711265.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-117543426-GGCC-G is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMX2	NM_004098.4	c.176_178del	p.Ala59del	inframe_deletion	1/3	ENST00000553456.5
EMX2OS	NR_002791.2	n.574+877_574+879del		intron_variant, non_coding_transcript_variant
EMX2	NM_001165924.2	c.176_178del	p.Ala59del	inframe_deletion	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMX2	ENST00000553456.5	c.176_178del	p.Ala59del	inframe_deletion	1/3	1	NM_004098.4	P1
EMX2OS	ENST00000551288.5	n.574+877_574+879del		intron_variant, non_coding_transcript_variant		1
EMX2	ENST00000442245.5	c.176_178del	p.Ala59del	inframe_deletion	1/2	2

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

GnomAD3 exomes AF: 0.000298 AC: 62 AN: 208116 Hom.: 0 AF XY: 0.000314 AC XY: 36 AN XY: 114474

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 SAS exome AF: 0.000143

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

Gnomad4 AFR exome AF: 0.0000605

Gnomad4 AMR exome AF: 0.000232

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.0000474

Gnomad4 FIN exome AF: 0.0000598

Gnomad4 NFE exome AF: 0.000253

Gnomad4 OTH exome AF: 0.000101

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

Gnomad4 AFR AF: 0.0000966

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000132

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

EMX2: PM4:Supporting, BS1 -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs756693906; hg19: chr10-119302937;