GeneBe

rs190091435

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_015267.4(CUX2):​c.81C>A​(p.Val27Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V27V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CUX2
NM_015267.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0730

Publications

1 publications found
Variant links:
Genes affected
CUX2 (HGNC:19347): (cut like homeobox 2) This gene encodes a protein which contains three CUT domains and a homeodomain; both domains are DNA-binding motifs. A similar gene, whose gene product possesses different DNA-binding activities, is located on chromosome on chromosome 7. Two pseudogenes of this gene have been identified on chromosomes 10 and 4. [provided by RefSeq, Jan 2013]
CUX2 Gene-Disease associations (from GenCC):
  • developmental and epileptic encephalopathy, 67
    Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
  • genetic developmental and epileptic encephalopathy
    Inheritance: AD Classification: MODERATE Submitted by: ClinGen
  • Lennox-Gastaut syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP7
Synonymous conserved (PhyloP=0.073 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015267.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CUX2
NM_015267.4
MANE Select
c.81C>Ap.Val27Val
synonymous
Exon 2 of 22NP_056082.2O14529
CUX2
NM_001370598.1
c.-106C>A
5_prime_UTR
Exon 2 of 22NP_001357527.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CUX2
ENST00000261726.11
TSL:1 MANE Select
c.81C>Ap.Val27Val
synonymous
Exon 2 of 22ENSP00000261726.6O14529
CUX2
ENST00000397643.3
TSL:1
c.261C>Ap.Val87Val
synonymous
Exon 3 of 8ENSP00000380765.3F5GWR6
CUX2
ENST00000933089.1
c.81C>Ap.Val27Val
synonymous
Exon 2 of 21ENSP00000603148.1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1393732
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
691800
African (AFR)
AF:
0.00
AC:
0
AN:
29750
American (AMR)
AF:
0.00
AC:
0
AN:
33010
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24104
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37134
South Asian (SAS)
AF:
0.00
AC:
0
AN:
75054
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52298
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5496
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1079556
Other (OTH)
AF:
0.00
AC:
0
AN:
57330
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
6.1
DANN
Benign
0.67
PhyloP100
0.073

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

Other links and lift over

dbSNP: rs190091435; hg19: chr12-111652021; API