Variant 5-10973669-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001332.4(CTNND2):c.3462C>T(p.Tyr1154Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,612,878 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 25 hom. )

Consequence

CTNND2
NM_001332.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.371

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:

CTNND2 (HGNC:):

CTNND2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 5-10973669-G-A is Benign according to our data. Variant chr5-10973669-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 724675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-10973669-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.371 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00187 (285/152280) while in subpopulation SAS AF= 0.00788 (38/4820). AF 95% confidence interval is 0.0059. There are 0 homozygotes in gnomad4. There are 129 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 285 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNND2	NM_001332.4 linkuse as main transcript	c.3462C>T	p.Tyr1154Tyr	synonymous_variant	22/22	ENST00000304623.13	NP_001323.1	Q9UQB3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNND2	ENST00000304623.13 linkuse as main transcript	c.3462C>T	p.Tyr1154Tyr	synonymous_variant	22/22	1	NM_001332.4	ENSP00000307134.8		Q9UQB3-1

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

285

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00788

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00259

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00264

AC:

654

AN:

247818

Hom.:

AF XY:

0.00299

AC XY:

401

AN XY:

134096

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00235

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00273

AC:

3983

AN:

1460598

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

2117

AN XY:

726552

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.00960

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00255

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.00187

AC:

285

AN:

152280

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

129

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00788

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00259

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00168

Hom.:

Bravo

AF:

0.00182

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.00294

EpiControl

AF:

0.00243

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	CTNND2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.3

DANN

Benign

0.47

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