Variant chr10-117543527-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004098.4(EMX2):c.260C>T(p.Pro87Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,578 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EMX2
NM_004098.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.44

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EMX2	NM_004098.4 linkuse as main transcript	c.260C>T	p.Pro87Leu	missense_variant	1/3	ENST00000553456.5	NP_004089.1
EMX2OS	NR_002791.2 linkuse as main transcript	n.574+779G>A		intron_variant, non_coding_transcript_variant
EMX2	NM_001165924.2 linkuse as main transcript	c.260C>T	p.Pro87Leu	missense_variant	1/2		NP_001159396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMX2	ENST00000553456.5 linkuse as main transcript	c.260C>T	p.Pro87Leu	missense_variant	1/3	1	NM_004098.4	ENSP00000450962	P1	Q04743-1
EMX2OS	ENST00000551288.5 linkuse as main transcript	n.574+779G>A		intron_variant, non_coding_transcript_variant		1
EMX2	ENST00000442245.5 linkuse as main transcript	c.260C>T	p.Pro87Leu	missense_variant	1/2	2		ENSP00000474874		Q04743-2
EMX2	ENST00000616794.1 linkuse as main transcript			upstream_gene_variant		2		ENSP00000480271

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151600

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458578

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725476

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151600

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74036

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000831

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Schizencephaly

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Mar 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.76

D;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D

M_CAP

Pathogenic

0.67

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Uncertain

0.15

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-4.2

D;.

REVEL

Uncertain

0.46

Sift

Uncertain

0.010

D;.

Sift4G

Benign

0.19

T;D

Polyphen

0.61

P;.

Vest4

0.43

MutPred

0.35

Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);

MVP

0.92

ClinPred

0.98

GERP RS

5.9

Varity_R

0.16

gMVP

0.78

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

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