2-176080374-C-A

Variant names:

• chr2-176080374-C-A
• rs757906013
• NM_001080458.2:c.1164G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001080458.2(EVX2):​c.1164G>T​(p.Ser388Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000492 in 1,219,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S388S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: EVX2 NM_001080458.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP7: Synonymous conserved (PhyloP=-0.118 with no splicing effect.

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.1164G>T	p.Ser388Ser	synonymous	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.1164G>T	p.Ser388Ser	synonymous	Exon 3 of 3	ENSP00000312385.4	Q03828

Frequencies

GnomAD3 genomes AF: 0.00000687 AC: 1 AN: 145540 Hom.: 0 Cov.: 30

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: 0.0000153

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000167 AC: 1 AN: 59808 AF XY: 0.0000280

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000466 AC: 5 AN: 1073706 Hom.: 0 Cov.: 32 AF XY: 0.00000573 AC XY: 3 AN XY: 523790

African (AFR) AF: 0.00 AC: 0 AN: 21448

American (AMR) AF: 0.00 AC: 0 AN: 16378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14908

East Asian (EAS) AF: 0.00 AC: 0 AN: 16968

South Asian (SAS) AF: 0.0000902 AC: 4 AN: 44332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2746

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 900052

Other (OTH) AF: 0.00 AC: 0 AN: 39974

GnomAD4 genome AF: 0.00000687 AC: 1 AN: 145540 Hom.: 0 Cov.: 30 AF XY: 0.0000141 AC XY: 1 AN XY: 70814

African (AFR) AF: 0.00 AC: 0 AN: 40320

American (AMR) AF: 0.00 AC: 0 AN: 14852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3368

East Asian (EAS) AF: 0.00 AC: 0 AN: 4876

South Asian (SAS) AF: 0.00 AC: 0 AN: 4742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65450

Other (OTH) AF: 0.00 AC: 0 AN: 2016

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		-0.12
Mutation Taster		=100/0	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: rs757906013; hg19: chr2-176945102;