Genetic Variant EMX2:c.592-52T>A (chr10-117548013-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004098.4(EMX2):c.592-52T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,566,696 control chromosomes in the GnomAD database, including 289,280 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 22116 hom., cov: 30)

Exomes 𝑓: 0.61 ( 267164 hom. )

Consequence

EMX2
NM_004098.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.619

Publications

13 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 Gene-Disease associations (from GenCC):

schizencephaly
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

EMX2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	NM_004098.4	MANE Select	c.592-52T>A		intron	N/A	NP_004089.1	Q04743-1
	EMX2	NM_001165924.2		c.407-52T>A		intron	N/A	NP_001159396.1	Q04743-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EMX2	ENST00000553456.5	TSL:1 MANE Select	c.592-52T>A	intron	N/A	ENSP00000450962.3	Q04743-1
EMX2	ENST00000546446.2	TSL:1	n.551-52T>A	intron	N/A
EMX2	ENST00000442245.5	TSL:2	c.407-52T>A	intron	N/A	ENSP00000474874.1	Q04743-2

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

78803

AN:

151672

Hom.:

22110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.647

Gnomad AMR

AF:

0.573

Gnomad ASJ

AF:

0.552

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.561

Gnomad MID

AF:

0.637

Gnomad NFE

AF:

0.629

Gnomad OTH

AF:

0.582

GnomAD4 exome

AF:

0.610

AC:

862952

AN:

1414906

Hom.:

267164

Cov.:

AF XY:

0.607

AC XY:

424539

AN XY:

699608

show subpopulations

African (AFR)

AF:

0.290

AC:

9440

AN:

32508

American (AMR)

AF:

0.581

AC:

21979

AN:

37854

Ashkenazi Jewish (ASJ)

AF:

0.547

AC:

13885

AN:

25362

East Asian (EAS)

AF:

0.543

AC:

20407

AN:

37548

South Asian (SAS)

AF:

0.461

AC:

37077

AN:

80450

European-Finnish (FIN)

AF:

0.570

AC:

27070

AN:

47512

Middle Eastern (MID)

AF:

0.587

AC:

3251

AN:

5542

European-Non Finnish (NFE)

AF:

0.639

AC:

695512

AN:

1089216

Other (OTH)

AF:

0.583

AC:

34331

AN:

58914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

18810

37621

56431

75242

94052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18444

36888

55332

73776

92220

<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

AF:

0.519

AC:

78835

AN:

151790

Hom.:

22116

Cov.:

AF XY:

0.515

AC XY:

38236

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.303

AC:

12521

AN:

41364

American (AMR)

AF:

0.572

AC:

8728

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.552

AC:

1916

AN:

3468

East Asian (EAS)

AF:

0.560

AC:

2866

AN:

5114

South Asian (SAS)

AF:

0.441

AC:

2118

AN:

4798

European-Finnish (FIN)

AF:

0.561

AC:

5923

AN:

10552

Middle Eastern (MID)

AF:

0.627

AC:

183

AN:

292

European-Non Finnish (NFE)

AF:

0.630

AC:

42760

AN:

67926

Other (OTH)

AF:

0.585

AC:

1231

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1775

3550

5324

7099

8874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.563

Hom.:

3063

Bravo

AF:

0.519

Asia WGS

AF:

0.445

AC:

1549

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.80

(source)

DANN

Benign

0.51

PhyloP100

-0.62

Mutation Taster

=100/0

polymorphism (auto)

(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

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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