rs202171958
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_004098.4(EMX2):c.591+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
EMX2
NM_004098.4 splice_donor_region, intron
NM_004098.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.002863
2
Clinical Significance
Conservation
PhyloP100: -1.41
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 Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 10-117545822-T-C is Benign according to our data. Variant chr10-117545822-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 585848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EMX2 | NM_004098.4 | c.591+6T>C | splice_donor_region_variant, intron_variant | ENST00000553456.5 | |||
EMX2 | NM_001165924.2 | c.406+2149T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EMX2 | ENST00000553456.5 | c.591+6T>C | splice_donor_region_variant, intron_variant | 1 | NM_004098.4 | P1 | |||
EMX2 | ENST00000546446.2 | n.550+6T>C | splice_donor_region_variant, intron_variant, non_coding_transcript_variant | 1 | |||||
EMX2 | ENST00000442245.5 | c.406+2149T>C | intron_variant | 2 | |||||
EMX2 | ENST00000616794.1 | c.106+2149T>C | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152148Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000441 AC: 110AN: 249170Hom.: 0 AF XY: 0.000392 AC XY: 53AN XY: 135116
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GnomAD4 exome AF: 0.000116 AC: 170AN: 1461406Hom.: 0 Cov.: 32 AF XY: 0.000109 AC XY: 79AN XY: 727012
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GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152266Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74458
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 30, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at