Genetic Variant EMX2:p.Asn80His (chr10-117543505-A-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_004098.4(EMX2):c.238A>C(p.Asn80His) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N80K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00071 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EMX2
NM_004098.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.80

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26533034).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMX2	NM_004098.4	MANE Select	c.238A>C	p.Asn80His	missense	Exon 1 of 3	NP_004089.1	Q04743-1
EMX2	NM_001165924.2		c.238A>C	p.Asn80His	missense	Exon 1 of 2	NP_001159396.1	Q04743-2
EMX2OS	NR_002791.2		n.574+801T>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMX2	ENST00000553456.5	TSL:1 MANE Select	c.238A>C	p.Asn80His	missense	Exon 1 of 3	ENSP00000450962.3	Q04743-1
EMX2OS	ENST00000551288.5	TSL:1	n.574+801T>G		intron	N/A
EMX2	ENST00000442245.5	TSL:2	c.238A>C	p.Asn80His	missense	Exon 1 of 2	ENSP00000474874.1	Q04743-2

Frequencies

GnomAD3 genomes

AF:

0.000802

AC:

AN:

104694

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000671

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000706

Gnomad ASJ

AF:

0.000374

Gnomad EAS

AF:

0.000270

Gnomad SAS

AF:

0.000619

Gnomad FIN

AF:

0.00127

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000910

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000626

AC:

141

AN:

225260

AF XY:

0.000589

show subpopulations

Gnomad AFR exome

AF:

0.000289

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.000778

Gnomad EAS exome

AF:

0.00146

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000468

Gnomad OTH exome

AF:

0.000554

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000705

AC:

798

AN:

1131282

Hom.:

Cov.:

AF XY:

0.000784

AC XY:

440

AN XY:

561408

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000745

AC:

AN:

25504

American (AMR)

AF:

0.00344

AC:

123

AN:

35744

Ashkenazi Jewish (ASJ)

AF:

0.00181

AC:

AN:

18234

East Asian (EAS)

AF:

0.00254

AC:

AN:

23262

South Asian (SAS)

AF:

0.00245

AC:

180

AN:

73548

European-Finnish (FIN)

AF:

0.000939

AC:

AN:

33006

Middle Eastern (MID)

AF:

0.000454

AC:

AN:

4402

European-Non Finnish (NFE)

AF:

0.000359

AC:

314

AN:

874268

Other (OTH)

AF:

0.000854

AC:

AN:

43314

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.237

Heterozygous variant carriers

138

276

415

553

691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000802

AC:

AN:

104758

Hom.:

Cov.:

AF XY:

0.000756

AC XY:

AN XY:

50290

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000669

AC:

AN:

26892

American (AMR)

AF:

0.000705

AC:

AN:

9934

Ashkenazi Jewish (ASJ)

AF:

0.000374

AC:

AN:

2674

East Asian (EAS)

AF:

0.000271

AC:

AN:

3690

South Asian (SAS)

AF:

0.000622

AC:

AN:

3216

European-Finnish (FIN)

AF:

0.00127

AC:

AN:

5492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.000910

AC:

AN:

50532

Other (OTH)

AF:

0.00142

AC:

AN:

1404

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.246

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00521

Hom.:

ExAC

AF:

0.0000335

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.31

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.35

MutationAssessor

Benign

0.0

PhyloP100

4.8

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.38

Sift

Benign

0.12

Sift4G

Benign

0.14

Polyphen

0.69

Vest4

0.27

MutPred

0.21

Gain of catalytic residue at N80 (P = 0.2247)

MVP

0.90

ClinPred

0.021

GERP RS

4.8

PromoterAI

0.050

Neutral

(source)

Varity_R

0.24

gMVP

0.68

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over