Genetic Variant CTNND2:c.3417+177_3417+186dupGTGTGTGTGT (chr5-10981586-A-AACACACACAC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001332.4(CTNND2):c.3417+177_3417+186dupGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 40 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP6

Variant 5-10981586-A-AACACACACAC is Benign according to our data. Variant chr5-10981586-A-AACACACACAC is described in ClinVar as Benign. ClinVar VariationId is 1288595.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0164 (2472/150468) while in subpopulation NFE AF = 0.0199 (1342/67504). AF 95% confidence interval is 0.019. There are 40 homozygotes in GnomAd4. There are 1341 alleles in the male GnomAd4 subpopulation. Median coverage is 20. This position passed quality control check.

BS2

High AC in GnomAd4 at 2472 AD gene.

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+177_3417+186dupGTGTGTGTGT	intron	N/A	NP_001323.1	Q9UQB3-1
CTNND2	NM_001288715.1		c.3144+177_3144+186dupGTGTGTGTGT	intron	N/A	NP_001275644.1	Q9UQB3
CTNND2	NM_001364128.2		c.2481+177_2481+186dupGTGTGTGTGT	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+187insGTGTGTGTGT	intron	N/A	ENSP00000307134.8	Q9UQB3-1
CTNND2	ENST00000511377.5	TSL:1	c.3144+186_3144+187insGTGTGTGTGT	intron	N/A	ENSP00000426510.1	E7EPC8
CTNND2	ENST00000513588.5	TSL:1	n.119+186_119+187insGTGTGTGTGT	intron	N/A	ENSP00000421093.1	E9PHB5

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2470

AN:

150358

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00383

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00996

Gnomad ASJ

AF:

0.00669

Gnomad EAS

AF:

0.00624

Gnomad SAS

AF:

0.0159

Gnomad FIN

AF:

0.0642

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0199

Gnomad OTH

AF:

0.0156

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

GnomAD4 genome

AF:

0.0164

AC:

2472

AN:

150468

Hom.:

Cov.:

AF XY:

0.0183

AC XY:

1341

AN XY:

73432

show subpopulations

African (AFR)

AF:

0.00384

AC:

158

AN:

41112

American (AMR)

AF:

0.00995

AC:

150

AN:

15072

Ashkenazi Jewish (ASJ)

AF:

0.00669

AC:

AN:

3440

East Asian (EAS)

AF:

0.00625

AC:

AN:

5122

South Asian (SAS)

AF:

0.0160

AC:

AN:

4758

European-Finnish (FIN)

AF:

0.0642

AC:

654

AN:

10186

Middle Eastern (MID)

AF:

0.00690

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0199

AC:

1342

AN:

67504

Other (OTH)

AF:

0.0169

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

111

221

332

442

553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0102

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

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

5-10981586-AACACACAC-AACACACACACACACACAC

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