Genetic Variant CTNND2:c.3417+185_3417+186dupGT (chr5-10981586-A-AAC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001332.4(CTNND2):c.3417+185_3417+186dupGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 1594 hom., cov: 20)

Consequence

CTNND2
NM_001332.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.53

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Illumina
neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: G2P
benign adult familial myoclonic epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CTNND2 links:

LOC105374654 (HGNC:):

LOC105374654 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 5-10981586-A-AAC is Benign according to our data. Variant chr5-10981586-A-AAC is described in ClinVar as Benign. ClinVar VariationId is 1253470.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001332.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTNND2	NM_001332.4	MANE Select	c.3417+185_3417+186dupGT	intron	N/A	NP_001323.1	Q9UQB3-1
CTNND2	NM_001288715.1		c.3144+185_3144+186dupGT	intron	N/A	NP_001275644.1	Q9UQB3
CTNND2	NM_001364128.2		c.2481+185_2481+186dupGT	intron	N/A	NP_001351057.1	A0A994J5V2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTNND2	ENST00000304623.13	TSL:1 MANE Select	c.3417+186_3417+187insGT	intron	N/A	ENSP00000307134.8	Q9UQB3-1
CTNND2	ENST00000511377.5	TSL:1	c.3144+186_3144+187insGT	intron	N/A	ENSP00000426510.1	E7EPC8
CTNND2	ENST00000513588.5	TSL:1	n.119+186_119+187insGT	intron	N/A	ENSP00000421093.1	E9PHB5

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

21810

AN:

150290

Hom.:

1591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.00624

Gnomad SAS

AF:

0.0432

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.151

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.145

AC:

21847

AN:

150400

Hom.:

1594

Cov.:

AF XY:

0.143

AC XY:

10504

AN XY:

73394

show subpopulations

African (AFR)

AF:

0.181

AC:

7437

AN:

41088

American (AMR)

AF:

0.125

AC:

1883

AN:

15066

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

743

AN:

3440

East Asian (EAS)

AF:

0.00625

AC:

AN:

5122

South Asian (SAS)

AF:

0.0431

AC:

205

AN:

4758

European-Finnish (FIN)

AF:

0.132

AC:

1340

AN:

10176

Middle Eastern (MID)

AF:

0.141

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.144

AC:

9719

AN:

67480

Other (OTH)

AF:

0.151

AC:

312

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

924

1848

2771

3695

4619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0413

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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5-10981586-AACACACAC-AACACACACAC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over