rs3809282

Variant names:

• chr12-111269993-C-T
• rs3809282
• NM_015267.4:c.301+6154C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015267.4(CUX2):​c.301+6154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 152,224 control chromosomes in the GnomAD database, including 217 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 0.028 (217 hom., cov: 32)
• Consequence: CUX2 NM_015267.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUX2	NM_015267.4	c.301+6154C>T		intron_variant	Intron 4 of 21	ENST00000261726.11	NP_056082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUX2	ENST00000261726.11	c.301+6154C>T		intron_variant	Intron 4 of 21	1	NM_015267.4	ENSP00000261726.6
CUX2	ENST00000397643.3	c.481+6154C>T		intron_variant	Intron 5 of 7	1		ENSP00000380765.3
CUX2	ENST00000551604.2	n.138-237C>T		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4307 AN: 152106 Hom.: 216 Cov.: 32

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.0956

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0196

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0283 AC: 4311 AN: 152224 Hom.: 217 Cov.: 32 AF XY: 0.0316 AC XY: 2355 AN XY: 74440

African (AFR) AF: 0.0423 AC: 1756 AN: 41520

American (AMR) AF: 0.0457 AC: 699 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1149 AN: 5180

South Asian (SAS) AF: 0.0953 AC: 459 AN: 4818

European-Finnish (FIN) AF: 0.0123 AC: 130 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68016

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.0134 Hom.: 309

Bravo AF: 0.0326

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3809282; hg19: chr12-111707797;