rs385209

Positions:

• chr10-117544545-T-C
• chr10-117544545-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.406+872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,058 control chromosomes in the GnomAD database, including 29,088 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 0.62 (29088 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: EMX2 NM_004098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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]

EMX2OS (HGNC:18511): (EMX2 opposite strand/antisense RNA)

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 (NFE) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMX2	NM_004098.4	c.406+872T>C		intron_variant		ENST00000553456.5	NP_004089.1
EMX2OS	NR_002791.2	n.503+21A>G		intron_variant, non_coding_transcript_variant
EMX2	NM_001165924.2	c.406+872T>C		intron_variant			NP_001159396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMX2	ENST00000553456.5	c.406+872T>C		intron_variant		1	NM_004098.4	ENSP00000450962	P1
EMX2OS	ENST00000551288.5	n.503+21A>G		intron_variant, non_coding_transcript_variant		1
EMX2	ENST00000442245.5	c.406+872T>C		intron_variant		2		ENSP00000474874
EMX2	ENST00000616794.1	c.106+872T>C		intron_variant		2		ENSP00000480271

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93470 AN: 151938 Hom.: 29073 Cov.: 32

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.647

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.615 AC: 93527 AN: 152056 Hom.: 29088 Cov.: 32 AF XY: 0.608 AC XY: 45188 AN XY: 74308

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.649

Alfa AF: 0.635 Hom.: 14691

Bravo AF: 0.622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.37

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: rs385209; hg19: chr10-119304056;