dbSNP rs765655737: CTNND2:p.Pro268Leu (chr5-11385039-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001332.4(CTNND2):c.803C>T(p.Pro268Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000034 in 1,177,376 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P268Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

CTNND2
NM_001332.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.15

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]

CTNND2 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 rank	MANE	Protein	UniProt
CTNND2	NM_001332.4 link	c.803C>T	p.Pro268Leu	missense_variant	Exon 7 of 22	ENST00000304623.13	NP_001323.1	Q9UQB3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNND2	ENST00000304623.13 link	c.803C>T	p.Pro268Leu	missense_variant	Exon 7 of 22	1	NM_001332.4	ENSP00000307134.8		Q9UQB3-1

Frequencies

GnomAD3 genomes

AF:

0.00000676

AC:

AN:

147980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000291

AC:

AN:

1029396

Hom.:

Cov.:

AF XY:

0.00000408

AC XY:

AN XY:

489670

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000337

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000676

AC:

AN:

147980

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72060

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;T;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.65

T;T;T

M_CAP

Pathogenic

0.60

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Uncertain

0.33

MutationAssessor

Uncertain

2.2

M;.;.

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0040

D;D;.

Polyphen

1.0

D;.;.

Vest4

0.43

MutPred

0.27

Gain of stability (P = 0.047);.;.;

MVP

0.91

MPC

2.1

ClinPred

0.98

GERP RS

3.5

Varity_R

0.40

gMVP

0.60

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over