rs2240776

chr10-117548013-T-Achr10-117548013-T-Cchr10-117548013-T-G

Variant summary

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

The NM_004098.4(EMX2):c.592-52T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,566,696 control chromosomes in the GnomAD database, including 289,280 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 0.52 (22116 hom., cov: 30)
  • Exomes 𝑓: 0.61 (267164 hom.)
• Consequence: EMX2 NM_004098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619

Genes affected

EMX2 (HGNC:3341): (empty spiracles homeobox 2) This gene encodes a homeobox-containing transcription factor that is the homolog to the 'empty spiracles' gene in Drosophila. Research on this gene in humans has focused on its expression in three tissues: dorsal telencephalon, olfactory neuroepithelium, and urogenetial system. It is expressed in the dorsal telencephalon during development in a low rostral-lateral to high caudal-medial gradient and is proposed to pattern the neocortex into defined functional areas. It is also expressed in embryonic and adult olfactory neuroepithelia where it complexes with eukaryotic translation initiation factor 4E (eIF4E) and possibly regulates mRNA transport or translation. In the developing urogenital system, it is expressed in epithelial tissues and is negatively regulated by HOXA10. Alternative splicing results in multiple transcript variants encoding distinct proteins.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMX2	NM_004098.4	c.592-52T>A		intron_variant		ENST00000553456.5
EMX2	NM_001165924.2	c.407-52T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMX2	ENST00000553456.5	c.592-52T>A		intron_variant		1	NM_004098.4	P1
EMX2	ENST00000546446.2	n.551-52T>A		intron_variant, non_coding_transcript_variant		1
EMX2	ENST00000442245.5	c.407-52T>A		intron_variant		2
EMX2	ENST00000616794.1	c.107-52T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78803 AN: 151672 Hom.: 22110 Cov.: 30

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 0.610 AC: 862952 AN: 1414906 Hom.: 267164 Cov.: 34 AF XY: 0.607 AC XY: 424539 AN XY: 699608

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.581

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.543

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.570

Gnomad4 NFE exome AF: 0.639

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.519 AC: 78835 AN: 151790 Hom.: 22116 Cov.: 30 AF XY: 0.515 AC XY: 38236 AN XY: 74194

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.585

Alfa AF: 0.563 Hom.: 3063

Bravo AF: 0.519

Asia WGS AF: 0.445 AC: 1549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.80
Dann	Benign	0.51

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: rs2240776; hg19: chr10-119307524; COSMIC: COSV71294729; COSMIC: COSV71294729;