chr2-176080421-C-G

Variant summary

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

The NM_001080458.2(EVX2):​c.1117G>C​(p.Ala373Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000369 in 1,083,178 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EVX2
NM_001080458.2 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
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]

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 rank MANE Protein UniProt
EVX2NM_001080458.2 linkc.1117G>C p.Ala373Pro missense_variant Exon 3 of 3 ENST00000308618.5 NP_001073927.1 Q03828

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EVX2ENST00000308618.5 linkc.1117G>C p.Ala373Pro missense_variant Exon 3 of 3 5 NM_001080458.2 ENSP00000312385.4 Q03828

Frequencies

GnomAD3 genomes
AF:
0.0000138
AC:
2
AN:
145214
Hom.:
0
Cov.:
30
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:
0.000411
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:
0.00000213
AC:
2
AN:
937964
Hom.:
0
Cov.:
32
AF XY:
0.00000227
AC XY:
1
AN XY:
441194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000159
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000138
AC:
2
AN:
145214
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
70686
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000411
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1117G>C (p.A373P) alteration is located in exon 3 (coding exon 3) of the EVX2 gene. This alteration results from a G to C substitution at nucleotide position 1117, causing the alanine (A) at amino acid position 373 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Uncertain
0.058
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
16
DANN
Benign
0.94
DEOGEN2
Benign
0.10
T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.25
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.45
T
M_CAP
Pathogenic
0.96
D
MetaRNN
Uncertain
0.55
D
MetaSVM
Uncertain
0.25
D
MutationAssessor
Benign
0.69
N
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
0.60
N
REVEL
Uncertain
0.33
Sift
Benign
0.18
T
Sift4G
Benign
0.22
T
Polyphen
0.98
D
Vest4
0.42
MutPred
0.29
Loss of helix (P = 0.0068);
MVP
0.91
ClinPred
0.40
T
GERP RS
3.7
Varity_R
0.30
gMVP
0.83

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.

Other links and lift over

dbSNP: rs1174200306; hg19: chr2-176945149; API