rs1034603

Positions:

• chr12-111211540-A-G
• chr12-111211540-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015267.4(CUX2):​c.64-2660A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,188 control chromosomes in the GnomAD database, including 3,084 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 0.18 (3084 hom., cov: 32)
• Consequence: CUX2 NM_015267.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUX2	NM_015267.4	c.64-2660A>G		intron_variant		ENST00000261726.11	NP_056082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUX2	ENST00000261726.11	c.64-2660A>G		intron_variant		1	NM_015267.4	ENSP00000261726	P1
CUX2	ENST00000397643.3	c.244-2660A>G		intron_variant		1		ENSP00000380765

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27087 AN: 152070 Hom.: 3090 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.178 AC: 27107 AN: 152188 Hom.: 3084 Cov.: 32 AF XY: 0.183 AC XY: 13627 AN XY: 74416

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0525

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.157

Alfa AF: 0.134 Hom.: 884

Bravo AF: 0.177

Asia WGS AF: 0.372 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.17
DANN	Benign	0.37

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

LitVar

Other links and lift over

dbSNP: rs1034603; hg19: chr12-111649344;