10-117543372-A-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004098.4(EMX2):c.105A>T(p.Ala35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000426 in 1,571,416 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00070 (1 hom., cov: 29)
  • Exomes 𝑓: 0.00040 (4 hom.)
• Consequence: EMX2 NM_004098.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.178

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 10-117543372-A-T is Benign according to our data. Variant chr10-117543372-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 193271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.178 with no splicing effect.
• BS2: High AC in GnomAd at 105 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMX2	NM_004098.4	c.105A>T	p.Ala35=	synonymous_variant	1/3	ENST00000553456.5
EMX2OS	NR_002791.2	n.574+934T>A		intron_variant, non_coding_transcript_variant
EMX2	NM_001165924.2	c.105A>T	p.Ala35=	synonymous_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMX2	ENST00000553456.5	c.105A>T	p.Ala35=	synonymous_variant	1/3	1	NM_004098.4	P1
EMX2OS	ENST00000551288.5	n.574+934T>A		intron_variant, non_coding_transcript_variant		1
EMX2	ENST00000442245.5	c.105A>T	p.Ala35=	synonymous_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.000692 AC: 105 AN: 151692 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.000509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00446

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000884

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.00185 AC: 328 AN: 177430 Hom.: 1 AF XY: 0.00140 AC XY: 134 AN XY: 95968

Gnomad AFR exome AF: 0.000635

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00133

Gnomad SAS exome AF: 0.0000405

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000411

Gnomad OTH exome AF: 0.00211

GnomAD4 exome AF: 0.000397 AC: 564 AN: 1419614 Hom.: 4 Cov.: 32 AF XY: 0.000377 AC XY: 265 AN XY: 702478

Gnomad4 AFR exome AF: 0.000372

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00163

Gnomad4 SAS exome AF: 0.000135

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000339

Gnomad4 OTH exome AF: 0.000442

GnomAD4 genome AF: 0.000698 AC: 106 AN: 151802 Hom.: 1 Cov.: 29 AF XY: 0.000687 AC XY: 51 AN XY: 74198

Gnomad4 AFR AF: 0.000507

Gnomad4 AMR AF: 0.00452

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000884

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.000335 Hom.: 0

Bravo AF: 0.00110

Asia WGS AF: 0.00231 AC: 8 AN: 3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Nov 04, 2014

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	10
Dann	Benign	0.91

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: rs373030604; hg19: chr10-119302883;