Genetic Variant EVX2:p.Asp436His (chr2-176080232-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001080458.2(EVX2):c.1306G>C(p.Asp436His) variant causes a missense change. The variant allele was found at a frequency of 0.00000494 in 1,415,686 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D436G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

EVX2
NM_001080458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

Publications

0 publications found

Variant links:

Genes affected

EVX2 (HGNC:3507): (even-skipped homeobox 2) This gene is located at the 5' end of the HOXD gene cluster on chromosome 2. The encoded protein is a homeobox transcription factor that is related to the protein encoded by the Drosophila even-skipped (eve) gene, a member of the pair-rule class of segmentation genes. A 117 kb microdeletion at the 5' end of the HOXD gene cluster, which includes this gene and the HOXD9-HOXD13 genes, causes synpolydactyly, a dominantly inherited disease resulting in limb malformation. [provided by RefSeq, Sep 2009]

EVX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080458.2. 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
	EVX2	NM_001080458.2	MANE Select	c.1306G>C	p.Asp436His	missense	Exon 3 of 3	NP_001073927.1	Q03828

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVX2	ENST00000308618.5	TSL:5 MANE Select	c.1306G>C	p.Asp436His	missense	Exon 3 of 3	ENSP00000312385.4	Q03828

Frequencies

GnomAD3 genomes

AF:

0.0000398

AC:

AN:

150912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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

GnomAD2 exomes

AF:

0.00

AC:

AN:

73014

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

AF:

7.91e-7

AC:

AN:

1264774

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

623030

show subpopulations

African (AFR)

AF:

0.0000381

AC:

AN:

26242

American (AMR)

AF:

0.00

AC:

AN:

24096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21656

East Asian (EAS)

AF:

0.00

AC:

AN:

27398

South Asian (SAS)

AF:

0.00

AC:

AN:

65398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3642

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1012790

Other (OTH)

AF:

0.00

AC:

AN:

51246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

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

AF:

0.0000398

AC:

AN:

150912

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73662

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41270

American (AMR)

AF:

0.00

AC:

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5058

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67528

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.95

MetaRNN

Uncertain

0.54

MetaSVM

Uncertain

0.59

MutationAssessor

Benign

1.7

PhyloP100

4.7

PrimateAI

Pathogenic

0.96

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.25

MutPred

0.15

Loss of phosphorylation at S440 (P = 0.1235)

MVP

0.86

ClinPred

0.99

GERP RS

2.8

Varity_R

0.74

gMVP

0.60

Mutation Taster

=24/76

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over