dbSNP rs201254067: CUX2:c.64-10A>G (chr12-111214190-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015267.4(CUX2):c.64-10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.0 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CUX2
NM_015267.4 intron

Scores

Splicing: ADA: 0.0005189

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.82

Publications

0 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

CUX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUX2	NM_015267.4	MANE Select	c.64-10A>G		intron	N/A	NP_056082.2	O14529
	CUX2	NM_001370598.1		c.-123-10A>G		intron	N/A	NP_001357527.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CUX2	ENST00000261726.11	TSL:1 MANE Select	c.64-10A>G	intron	N/A	ENSP00000261726.6	O14529
CUX2	ENST00000397643.3	TSL:1	c.244-10A>G	intron	N/A	ENSP00000380765.3	F5GWR6
CUX2	ENST00000933089.1		c.64-10A>G	intron	N/A	ENSP00000603148.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

74522

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000382

AC:

AN:

784840

Hom.:

Cov.:

AF XY:

0.00000260

AC XY:

AN XY:

384868

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

14558

American (AMR)

AF:

0.00

AC:

AN:

12142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12882

East Asian (EAS)

AF:

0.00

AC:

AN:

22422

South Asian (SAS)

AF:

0.00

AC:

AN:

27034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30640

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2882

European-Non Finnish (NFE)

AF:

0.00000476

AC:

AN:

629994

Other (OTH)

AF:

0.00

AC:

AN:

32286

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0763859), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

74522

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

36444

African (AFR)

AF:

0.00

AC:

AN:

17914

American (AMR)

AF:

0.00

AC:

AN:

7698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1960

East Asian (EAS)

AF:

0.00

AC:

AN:

2552

South Asian (SAS)

AF:

0.00

AC:

AN:

2382

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

180

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

35550

Other (OTH)

AF:

0.00

AC:

AN:

998

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00052

dbscSNV1_RF

Benign

0.076

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over