10-117543426-G-GGCC

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BP6BS2

The NM_004098.4(EMX2):c.176_178dupCCG(p.Ala59dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000538 in 1,597,602 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

EMX2
NM_004098.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.70

Variant links:

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]

EMX2 links:

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

EMX2OS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_004098.4

BP6

Variant 10-117543426-G-GGCC is Benign according to our data. Variant chr10-117543426-G-GGCC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 290406.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMX2	NM_004098.4 link	c.176_178dupCCG	p.Ala59dup	disruptive_inframe_insertion	Exon 1 of 3	ENST00000553456.5	NP_004089.1	Q04743-1
EMX2	NM_001165924.2 link	c.176_178dupCCG	p.Ala59dup	disruptive_inframe_insertion	Exon 1 of 2		NP_001159396.1	Q04743-2
EMX2OS	NR_002791.2 link	n.574+877_574+879dupGGC		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EMX2	ENST00000553456.5 link	c.176_178dupCCG	p.Ala59dup	disruptive_inframe_insertion	Exon 1 of 3	1	NM_004098.4	ENSP00000450962.3	Q04743-1
EMX2OS	ENST00000551288.5 link	n.574+877_574+879dupGGC		intron_variant	Intron 2 of 3	1
EMX2	ENST00000442245.5 link	c.176_178dupCCG	p.Ala59dup	disruptive_inframe_insertion	Exon 1 of 2	2		ENSP00000474874.1	Q04743-2
EMX2	ENST00000616794.1 link	c.-142_-141insGCC		upstream_gene_variant		2		ENSP00000480271.1	A0A087WWJ6

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151830

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000577

AC:

AN:

208116

Hom.:

AF XY:

0.0000524

AC XY:

AN XY:

114474

show subpopulations

Gnomad AFR exome

AF:

0.0000918

Gnomad AMR exome

AF:

0.0000631

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000642

Gnomad SAS exome

AF:

0.000179

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000112

Gnomad OTH exome

AF:

0.000382

GnomAD4 exome

AF:

0.0000553

AC:

AN:

1445772

Hom.:

Cov.:

AF XY:

0.0000515

AC XY:

AN XY:

717916

show subpopulations

Gnomad4 AFR exome

AF:

0.000181

Gnomad4 AMR exome

AF:

0.0000464

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.000154

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000480

Gnomad4 OTH exome

AF:

0.0000671

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151830

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.0000736

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Sep 13, 2016

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Jan 31, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over