Genetic Variant NM_015267.4:c.301+6815A>C (chr12-111270654-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015267.4(CUX2):c.301+6815A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,440 control chromosomes in the GnomAD database, including 9,219 homozygotes. 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 0.30 ( 9219 hom., cov: 30)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

CUX2
NM_015267.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.960

Publications

31 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUX2	NM_015267.4 link	c.301+6815A>C		intron_variant	Intron 4 of 21	ENST00000261726.11	NP_056082.2	O14529

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CUX2	ENST00000261726.11 link	c.301+6815A>C	intron_variant	Intron 4 of 21	1	NM_015267.4	ENSP00000261726.6	O14529
CUX2	ENST00000397643.3 link	c.481+6815A>C	intron_variant	Intron 5 of 7	1		ENSP00000380765.3	F5GWR6
CUX2	ENST00000551604.2 link	n.562A>C	splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45251

AN:

151310

Hom.:

9221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0757

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.271

Gnomad ASJ

AF:

0.636

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0860

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.325

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.299

AC:

45237

AN:

151432

Hom.:

9219

Cov.:

AF XY:

0.289

AC XY:

21375

AN XY:

73908

show subpopulations

African (AFR)

AF:

0.0755

AC:

3123

AN:

41380

American (AMR)

AF:

0.270

AC:

4116

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.636

AC:

2203

AN:

3466

East Asian (EAS)

AF:

0.00174

AC:

AN:

5180

South Asian (SAS)

AF:

0.0865

AC:

415

AN:

4798

European-Finnish (FIN)

AF:

0.388

AC:

3985

AN:

10258

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.446

AC:

30226

AN:

67818

Other (OTH)

AF:

0.322

AC:

676

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

1347

2694

4041

5388

6735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.394

Hom.:

29572

Bravo

AF:

0.284

Asia WGS

AF:

0.0510

AC:

178

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.77

(source)

DANN

Benign

0.86

PhyloP100

-0.96

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over