rs767632611

Variant names:

• chr2-176080223-A-C
• rs767632611
• NM_001080458.2:c.1315T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-176080223-A-C
• chr2-176080223-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001080458.2(EVX2):​c.1315T>G​(p.Cys439Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000776 in 1,288,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C439R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: EVX2 NM_001080458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.30
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855

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.1315T>G	p.Cys439Gly	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.1315T>G	p.Cys439Gly	missense	Exon 3 of 3	ENSP00000312385.4	Q03828

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.76e-7 AC: 1 AN: 1288320 Hom.: 0 Cov.: 31 AF XY: 0.00000157 AC XY: 1 AN XY: 635370

African (AFR) AF: 0.00 AC: 0 AN: 26636

American (AMR) AF: 0.0000392 AC: 1 AN: 25524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22326

East Asian (EAS) AF: 0.00 AC: 0 AN: 27760

South Asian (SAS) AF: 0.00 AC: 0 AN: 69320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1026124

Other (OTH) AF: 0.00 AC: 0 AN: 52404

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Uncertain	0.63	D
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.66	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Benign	1.7	L
PhyloP100		4.3
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-5.6	D
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.54
MutPred		0.54		Gain of glycosylation at S440 (P = 0.0483)
MVP		0.89
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.95
gMVP		0.41
Mutation Taster		=30/70	disease causing

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: rs767632611; hg19: chr2-176944951;