chr10-117545740-C-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_004098.4(EMX2):c.515C>A(p.Ala172Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
EMX2
NM_004098.4 missense
NM_004098.4 missense
Scores
9
5
2
Clinical Significance
Conservation
PhyloP100: 7.90
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.883
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EMX2 | NM_004098.4 | c.515C>A | p.Ala172Asp | missense_variant | 2/3 | ENST00000553456.5 | |
EMX2 | NM_001165924.2 | c.406+2067C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EMX2 | ENST00000553456.5 | c.515C>A | p.Ala172Asp | missense_variant | 2/3 | 1 | NM_004098.4 | P1 | |
EMX2 | ENST00000546446.2 | n.474C>A | non_coding_transcript_exon_variant | 2/3 | 1 | ||||
EMX2 | ENST00000442245.5 | c.406+2067C>A | intron_variant | 2 | |||||
EMX2 | ENST00000616794.1 | c.106+2067C>A | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 251026Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135846
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461736Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727172
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74368
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 14, 2023 | The c.515C>A (p.A172D) alteration is located in exon 2 (coding exon 2) of the EMX2 gene. This alteration results from a C to A substitution at nucleotide position 515, causing the alanine (A) at amino acid position 172 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.0788);
MVP
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at