Variant chr12-111217908-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015267.4(CUX2):c.193G>C(p.Ala65Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CUX2
NM_015267.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.31

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX2	NM_015267.4 linkuse as main transcript	c.193G>C	p.Ala65Pro	missense_variant	3/22	ENST00000261726.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CUX2	ENST00000261726.11 linkuse as main transcript	c.193G>C	p.Ala65Pro	missense_variant	3/22	1	NM_015267.4	P1
CUX2	ENST00000397643.3 linkuse as main transcript	c.373G>C	p.Ala125Pro	missense_variant	4/8	1
CUX2	ENST00000551604.2 linkuse as main transcript	n.29G>C		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

CUX2: PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;.

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.99

D;D

Vest4

0.58

MutPred

0.40

Gain of catalytic residue at A65 (P = 0.0364);.;

MVP

0.44

MPC

0.88

ClinPred

0.94

GERP RS

5.3

Varity_R

0.70

gMVP

0.73

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over