chr2-176080130-C-T

Variant names:

• chr2-176080130-C-T
• NM_001080458.2:c.1408G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080458.2(EVX2):​c.1408G>A​(p.Asp470Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. D470E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EVX2 NM_001080458.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52
• Publications: 0 publications found

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]

ACMG classification

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=0.32610977).

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.1408G>A	p.Asp470Asn	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.1408G>A	p.Asp470Asn	missense	Exon 3 of 3	ENSP00000312385.4	Q03828

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.19
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.90	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	0.69	N
PhyloP100		7.5
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.0030	B
Vest4		0.13
MutPred		0.099		Gain of helix (P = 0.1736)
MVP		0.78
ClinPred		0.96	D
GERP RS		1.9
Varity_R		0.29
gMVP		0.19
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

hg19: chr2-176944858;