2-176080234-G-A

Variant names:

• chr2-176080234-G-A
• rs1689114753
• NM_001080458.2:c.1304C>T

Variant summary

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

The NM_001080458.2(EVX2):​c.1304C>T​(p.Ser435Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EVX2 NM_001080458.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.86
• 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 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.1304C>T	p.Ser435Leu	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.1304C>T	p.Ser435Leu	missense	Exon 3 of 3	ENSP00000312385.4	Q03828

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1264048 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 622608

African (AFR) AF: 0.00 AC: 0 AN: 26212

American (AMR) AF: 0.00 AC: 0 AN: 24066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21634

East Asian (EAS) AF: 0.00 AC: 0 AN: 27398

South Asian (SAS) AF: 0.00 AC: 0 AN: 65236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3640

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1012362

Other (OTH) AF: 0.00 AC: 0 AN: 51214

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.27
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	0.040
Eigen_PC	Benign	0.011
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	1.6	L
PhyloP100		5.9
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.96	D
Vest4		0.29
MutPred		0.27		Loss of glycosylation at S435 (P = 9e-04)
MVP		0.83
ClinPred		0.90	D
GERP RS		2.8
Varity_R		0.24
gMVP		0.53
Mutation Taster		=60/40	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

dbSNP: rs1689114753; hg19: chr2-176944962;