Variant chr12-111214217-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_015267.4(CUX2):c.81C>T(p.Val27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,540,248 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0030 ( 11 hom. )

Consequence

CUX2
NM_015267.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0730

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 12-111214217-C-T is Benign according to our data. Variant chr12-111214217-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 713817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.073 with no splicing effect.

BS2

High AC in GnomAd4 at 361 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX2	NM_015267.4 linkuse as main transcript	c.81C>T	p.Val27=	synonymous_variant	2/22	ENST00000261726.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX2	ENST00000261726.11 linkuse as main transcript	c.81C>T	p.Val27=	synonymous_variant	2/22	1	NM_015267.4	P1
CUX2	ENST00000397643.3 linkuse as main transcript	c.261C>T	p.Val87=	synonymous_variant	3/8	1

Frequencies

GnomAD3 genomes

AF:

0.00246

AC:

361

AN:

146586

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000717

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00145

Gnomad EAS

AF:

0.000198

Gnomad SAS

AF:

0.000214

Gnomad FIN

AF:

0.00396

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00387

Gnomad OTH

AF:

0.00149

GnomAD3 exomes

AF:

0.00206

AC:

428

AN:

207294

Hom.:

AF XY:

0.00193

AC XY:

220

AN XY:

113696

show subpopulations

Gnomad AFR exome

AF:

0.000603

Gnomad AMR exome

AF:

0.00100

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00312

Gnomad NFE exome

AF:

0.00308

Gnomad OTH exome

AF:

0.00192

GnomAD4 exome

AF:

0.00300

AC:

4184

AN:

1393588

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

2061

AN XY:

691728

show subpopulations

Gnomad4 AFR exome

AF:

0.000739

Gnomad4 AMR exome

AF:

0.000879

Gnomad4 ASJ exome

AF:

0.000871

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000173

Gnomad4 FIN exome

AF:

0.00272

Gnomad4 NFE exome

AF:

0.00351

Gnomad4 OTH exome

AF:

0.00293

GnomAD4 genome

AF:

0.00246

AC:

361

AN:

146660

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

166

AN XY:

71112

show subpopulations

Gnomad4 AFR

AF:

0.000715

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00145

Gnomad4 EAS

AF:

0.000199

Gnomad4 SAS

AF:

0.000215

Gnomad4 FIN

AF:

0.00396

Gnomad4 NFE

AF:

0.00387

Gnomad4 OTH

AF:

0.00148

Alfa

AF:

0.00274

Hom.:

Bravo

AF:

0.00206

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	CUX2: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Developmental and epileptic encephalopathy, 67

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 14, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

8.6

DANN

Benign

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over