10-117545691-C-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BS1 BS2

The NM_004098.4(EMX2):c.466C>A(p.Arg156=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,614,126 control chromosomes in the GnomAD database, including 281 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (26 hom., cov: 33)
  • Exomes 𝑓: 0.017 (255 hom.)
• Consequence: EMX2 NM_004098.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.12

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 -11 ACMG points.

• BP6: Variant 10-117545691-C-A is Benign according to our data. Variant chr10-117545691-C-A is described in ClinVar as [Benign]. Clinvar id is 804789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.12 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0133 (2026/152356) while in subpopulation NFE AF= 0.0204 (1390/68028). AF 95% confidence interval is 0.0195. There are 26 homozygotes in gnomad4. There are 949 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 2028 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMX2	NM_004098.4	c.466C>A	p.Arg156=	synonymous_variant	2/3	ENST00000553456.5
EMX2	NM_001165924.2	c.406+2018C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMX2	ENST00000553456.5	c.466C>A	p.Arg156=	synonymous_variant	2/3	1	NM_004098.4	P1
EMX2	ENST00000546446.2	n.425C>A		non_coding_transcript_exon_variant	2/3	1
EMX2	ENST00000442245.5	c.406+2018C>A		intron_variant		2
EMX2	ENST00000616794.1	c.106+2018C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2028 AN: 152238 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.00289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0204

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.0139 AC: 3487 AN: 251056 Hom.: 36 AF XY: 0.0143 AC XY: 1944 AN XY: 135820

Gnomad AFR exome AF: 0.00246

Gnomad AMR exome AF: 0.00792

Gnomad ASJ exome AF: 0.0112

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0120

Gnomad FIN exome AF: 0.0197

Gnomad NFE exome AF: 0.0192

Gnomad OTH exome AF: 0.0149

GnomAD4 exome AF: 0.0173 AC: 25231 AN: 1461770 Hom.: 255 Cov.: 31 AF XY: 0.0172 AC XY: 12523 AN XY: 727188

Gnomad4 AFR exome AF: 0.00245

Gnomad4 AMR exome AF: 0.00894

Gnomad4 ASJ exome AF: 0.0105

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0117

Gnomad4 FIN exome AF: 0.0194

Gnomad4 NFE exome AF: 0.0192

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0133 AC: 2026 AN: 152356 Hom.: 26 Cov.: 33 AF XY: 0.0127 AC XY: 949 AN XY: 74504

Gnomad4 AFR AF: 0.00289

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00683

Gnomad4 FIN AF: 0.0186

Gnomad4 NFE AF: 0.0204

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.0174 Hom.: 13

Bravo AF: 0.0123

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0179

EpiControl AF: 0.0174

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Dec 27, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.040
Cadd	Benign	14
Dann	Benign	0.92

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: rs8192642; hg19: chr10-119305202;