rs8192640

Variant names:

• chr10-117545494-C-A
• rs8192640
• NM_004098.4:c.407-138C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-117545494-C-A
• chr10-117545494-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004098.4(EMX2):​c.407-138C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000109 in 920,102 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: EMX2 NM_004098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 0 publications found

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]

EMX2 Gene-Disease associations (from GenCC):

• schizencephaly

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004098.4. 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
	EMX2	NM_004098.4	MANE Select	c.407-138C>A		intron	N/A	NP_004089.1	Q04743-1
	EMX2	NM_001165924.2		c.406+1821C>A		intron	N/A	NP_001159396.1	Q04743-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	ENST00000553456.5	TSL:1 MANE Select	c.407-138C>A		intron	N/A	ENSP00000450962.3	Q04743-1
	EMX2	ENST00000546446.2	TSL:1	n.366-138C>A		intron	N/A
	EMX2	ENST00000442245.5	TSL:2	c.406+1821C>A		intron	N/A	ENSP00000474874.1	Q04743-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000109 AC: 1 AN: 920102 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 461306

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20638

American (AMR) AF: 0.00 AC: 0 AN: 22408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16980

East Asian (EAS) AF: 0.00 AC: 0 AN: 33110

South Asian (SAS) AF: 0.00 AC: 0 AN: 56876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2916

European-Non Finnish (NFE) AF: 0.00000147 AC: 1 AN: 681716

Other (OTH) AF: 0.00 AC: 0 AN: 41056

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.3
DANN	Benign	0.62
PhyloP100		-1.8

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: rs8192640; hg19: chr10-119305005;