2-176082509-C-T

Position:

• chr2-176082509-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080458.2(EVX2):​c.428-60G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,481,788 control chromosomes in the GnomAD database, including 97,385 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (13501 hom., cov: 34)
  • Exomes 𝑓: 0.35 (83884 hom.)
• Consequence: EVX2 NM_001080458.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVX2	NM_001080458.2	c.428-60G>A		intron_variant		ENST00000308618.5	NP_001073927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVX2	ENST00000308618.5	c.428-60G>A		intron_variant		5	NM_001080458.2	ENSP00000312385	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61680 AN: 152068 Hom.: 13473 Cov.: 34

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.350 AC: 465436 AN: 1329602 Hom.: 83884 AF XY: 0.352 AC XY: 228332 AN XY: 649576

Gnomad4 AFR exome AF: 0.540

Gnomad4 AMR exome AF: 0.558

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.435

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.335

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.406 AC: 61774 AN: 152186 Hom.: 13501 Cov.: 34 AF XY: 0.405 AC XY: 30125 AN XY: 74406

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.384

Alfa AF: 0.249 Hom.: 569

Bravo AF: 0.428

Asia WGS AF: 0.457 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.7
DANN	Benign	0.95

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

Other links and lift over

dbSNP: rs6758117; hg19: chr2-176947237;