Genetic Variant EMX2:p.Arg8Cys (chr10-117543289-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004098.4(EMX2):c.22C>T(p.Arg8Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. R8S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EMX2
NM_004098.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.71

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.847

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.22C>T	p.Arg8Cys	missense	Exon 1 of 3	NP_004089.1	Q04743-1
EMX2	NM_001165924.2		c.22C>T	p.Arg8Cys	missense	Exon 1 of 2	NP_001159396.1	Q04743-2
EMX2OS	NR_002791.2		n.574+1017G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMX2	ENST00000553456.5	TSL:1 MANE Select	c.22C>T	p.Arg8Cys	missense	Exon 1 of 3	ENSP00000450962.3	Q04743-1
EMX2OS	ENST00000551288.5	TSL:1	n.574+1017G>A		intron	N/A
EMX2	ENST00000442245.5	TSL:2	c.22C>T	p.Arg8Cys	missense	Exon 1 of 2	ENSP00000474874.1	Q04743-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

147916

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1397112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689092

African (AFR)

AF:

0.00

AC:

AN:

31486

American (AMR)

AF:

0.00

AC:

AN:

35680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25120

East Asian (EAS)

AF:

0.00

AC:

AN:

35646

South Asian (SAS)

AF:

0.00

AC:

AN:

79126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078434

Other (OTH)

AF:

0.00

AC:

AN:

57910

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.45

BayesDel_noAF

Pathogenic

0.41

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.89

MetaRNN

Pathogenic

0.85

MetaSVM

Pathogenic

0.80

MutationAssessor

Uncertain

2.2

PhyloP100

2.7

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-5.6

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.73

MutPred

0.51

Gain of sheet (P = 0.0827)

MVP

0.98

ClinPred

1.0

GERP RS

5.5

PromoterAI

-0.0092

Neutral

(source)

Varity_R

0.38

gMVP

0.79

Mutation Taster

=29/71

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over