Genetic Variant EVX2:p.Ala403Val (chr2-176080330-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001080458.2(EVX2):c.1208C>T(p.Ala403Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000039 in 1,281,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. A403E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

EVX2
NM_001080458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3167082).

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.1208C>T	p.Ala403Val	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.1208C>T	p.Ala403Val	missense	Exon 3 of 3	ENSP00000312385.4	Q03828

Frequencies

GnomAD3 genomes

AF:

0.00000680

AC:

AN:

147096

Hom.:

Cov.:

show subpopulations

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:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000144

AC:

AN:

69502

AF XY:

0.00

show subpopulations

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:

0.0000390

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000353

AC:

AN:

1134040

Hom.:

Cov.:

AF XY:

0.00000180

AC XY:

AN XY:

554414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23370

American (AMR)

AF:

0.00

AC:

AN:

20564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17226

East Asian (EAS)

AF:

0.00

AC:

AN:

21220

South Asian (SAS)

AF:

0.00

AC:

AN:

48626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21670

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3060

European-Non Finnish (NFE)

AF:

0.00000428

AC:

AN:

934750

Other (OTH)

AF:

0.00

AC:

AN:

43554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.00000680

AC:

AN:

147096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71658

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40684

American (AMR)

AF:

0.00

AC:

AN:

14924

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3390

East Asian (EAS)

AF:

0.00

AC:

AN:

4920

South Asian (SAS)

AF:

0.00

AC:

AN:

4760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

65988

Other (OTH)

AF:

0.00

AC:

AN:

2028

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

Alfa

AF:

0.00

Hom.:

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

Benign

0.25

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.85

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.50

MutationAssessor

Benign

0.0

PhyloP100

4.5

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.61

REVEL

Benign

0.26

Sift

Benign

0.082

Sift4G

Benign

0.30

Polyphen

0.42

Vest4

0.28

MutPred

0.40

Gain of catalytic residue at A403 (P = 0.0496)

MVP

0.85

ClinPred

0.16

GERP RS

3.0

Varity_R

0.10

gMVP

0.56

Mutation Taster

=94/6

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over