5-10973615-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001332.4(CTNND2):​c.3516C>A​(p.Phe1172Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

CTNND2
NM_001332.4 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.396
Variant links:
Genes affected
CTNND2 (HGNC:2516): (catenin delta 2) This gene encodes an adhesive junction associated protein of the armadillo/beta-catenin superfamily and is implicated in brain and eye development and cancer formation. The protein encoded by this gene promotes the disruption of E-cadherin based adherens junction to favor cell spreading upon stimulation by hepatocyte growth factor. This gene is overexpressed in prostate adenocarcinomas and is associated with decreased expression of tumor suppressor E-cadherin in this tissue. This gene resides in a region of the short arm of chromosome 5 that is deleted in Cri du Chat syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38141125).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTNND2NM_001332.4 linkc.3516C>A p.Phe1172Leu missense_variant Exon 22 of 22 ENST00000304623.13 NP_001323.1 Q9UQB3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTNND2ENST00000304623.13 linkc.3516C>A p.Phe1172Leu missense_variant Exon 22 of 22 1 NM_001332.4 ENSP00000307134.8 Q9UQB3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Uncertain
0.032
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.14
T;T;T;T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.44
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.85
T;T;T;T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.38
T;T;T;T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
0.81
L;.;.;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-1.2
N;N;.;N
REVEL
Uncertain
0.38
Sift
Benign
0.21
T;T;.;T
Sift4G
Benign
0.57
T;T;T;T
Polyphen
0.49
P;.;.;B
Vest4
0.33
MutPred
0.21
Loss of loop (P = 0.2237);.;.;.;
MVP
0.86
MPC
0.67
ClinPred
0.13
T
GERP RS
-0.85
Varity_R
0.085
gMVP
0.41

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.

Other links and lift over

dbSNP: rs1566622; hg19: chr5-10973727; API