Variant 12-111214215-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_015267.4(CUX2):c.79G>T(p.Val27Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000508 in 1,496,796 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V27I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00047 ( 1 hom., cov: 30)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

CUX2
NM_015267.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 3.09

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15313768).

BP6

Variant 12-111214215-G-T is Benign according to our data. Variant chr12-111214215-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1175839.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 64 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX2	NM_015267.4 linkuse as main transcript	c.79G>T	p.Val27Phe	missense_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.79G>T	p.Val27Phe	missense_variant	2/22	1	NM_015267.4	P1
CUX2	ENST00000397643.3 linkuse as main transcript	c.259G>T	p.Val87Phe	missense_variant	3/8	1

Frequencies

GnomAD3 genomes

AF:

0.000470

AC:

AN:

136190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000235

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:

0.000780

Gnomad OTH

AF:

0.000563

GnomAD3 exomes

AF:

0.000312

AC:

AN:

202220

Hom.:

AF XY:

0.000333

AC XY:

AN XY:

111174

show subpopulations

Gnomad AFR exome

AF:

0.000157

Gnomad AMR exome

AF:

0.000136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000363

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000475

Gnomad OTH exome

AF:

0.000663

GnomAD4 exome

AF:

0.000512

AC:

697

AN:

1360546

Hom.:

Cov.:

AF XY:

0.000479

AC XY:

323

AN XY:

674562

show subpopulations

Gnomad4 AFR exome

AF:

0.000139

Gnomad4 AMR exome

AF:

0.0000953

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000492

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000601

Gnomad4 OTH exome

AF:

0.000341

GnomAD4 genome

AF:

0.000470

AC:

AN:

136250

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

AN XY:

65004

show subpopulations

Gnomad4 AFR

AF:

0.000255

Gnomad4 AMR

AF:

0.000235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000780

Gnomad4 OTH

AF:

0.000556

Alfa

AF:

0.000598

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000613

AC:

ExAC

AF:

0.000265

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	CUX2: BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Developmental and epileptic encephalopathy, 67

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

May 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

0.68

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.4

N;D

REVEL

Benign

0.25

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

0.99

D;D

Vest4

0.33

MVP

0.42

MPC

1.5

ClinPred

0.074

GERP RS

5.6

Varity_R

0.29

gMVP

0.62

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