Variant chr5-10973721-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001332.4(CTNND2):c.3418-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,582,182 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 15 hom., cov: 33)

Exomes 𝑓: 0.00078 ( 19 hom. )

Consequence

CTNND2
NM_001332.4 splice_region, intron

Scores

Splicing: ADA: 0.00002141

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.09

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-10973721-G-A is Benign according to our data. Variant chr5-10973721-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 790009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00786 (1196/152216) while in subpopulation AFR AF= 0.0277 (1151/41528). AF 95% confidence interval is 0.0264. There are 15 homozygotes in gnomad4. There are 568 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1196 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNND2	NM_001332.4 linkuse as main transcript	c.3418-8C>T		splice_region_variant, intron_variant		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.3418-8C>T		splice_region_variant, intron_variant		1	NM_001332.4	ENSP00000307134.8		Q9UQB3-1

Frequencies

GnomAD3 genomes

AF:

0.00786

AC:

1196

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00229

AC:

500

AN:

218652

Hom.:

AF XY:

0.00174

AC XY:

203

AN XY:

116554

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000220

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000752

GnomAD4 exome

AF:

0.000783

AC:

1120

AN:

1429966

Hom.:

Cov.:

AF XY:

0.000692

AC XY:

490

AN XY:

707714

show subpopulations

Gnomad4 AFR exome

AF:

0.0297

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000176

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000456

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00786

AC:

1196

AN:

152216

Hom.:

Cov.:

AF XY:

0.00763

AC XY:

568

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0277

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00476

Hom.:

Bravo

AF:

0.00886

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 22, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

DANN

Benign

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0

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