Genetic Variant CTNND2:c.3417+181_3417+186dupGTGTGT (chr5-10981586-A-AACACAC) – 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+181_3417+186dupGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 849 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-AACACAC is Benign according to our data. Variant chr5-10981586-A-AACACAC is described in ClinVar as Benign. ClinVar VariationId is 1183085.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 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+181_3417+186dupGTGTGT	intron	N/A	NP_001323.1	Q9UQB3-1
CTNND2	NM_001288715.1		c.3144+181_3144+186dupGTGTGT	intron	N/A	NP_001275644.1	Q9UQB3
CTNND2	NM_001364128.2		c.2481+181_2481+186dupGTGTGT	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+187insGTGTGT	intron	N/A	ENSP00000307134.8	Q9UQB3-1
CTNND2	ENST00000511377.5	TSL:1	c.3144+186_3144+187insGTGTGT	intron	N/A	ENSP00000426510.1	E7EPC8
CTNND2	ENST00000513588.5	TSL:1	n.119+186_119+187insGTGTGT	intron	N/A	ENSP00000421093.1	E9PHB5

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15255

AN:

150276

Hom.:

848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0764

Gnomad ASJ

AF:

0.0831

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.0703

Gnomad FIN

AF:

0.0859

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0836

Gnomad OTH

AF:

0.0899

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

GnomAD4 genome

AF:

0.102

AC:

15268

AN:

150384

Hom.:

849

Cov.:

AF XY:

0.0999

AC XY:

7331

AN XY:

73394

show subpopulations

African (AFR)

AF:

0.138

AC:

5685

AN:

41068

American (AMR)

AF:

0.0770

AC:

1160

AN:

15074

Ashkenazi Jewish (ASJ)

AF:

0.0831

AC:

286

AN:

3440

East Asian (EAS)

AF:

0.192

AC:

980

AN:

5108

South Asian (SAS)

AF:

0.0698

AC:

332

AN:

4758

European-Finnish (FIN)

AF:

0.0859

AC:

875

AN:

10184

Middle Eastern (MID)

AF:

0.0621

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0836

AC:

5642

AN:

67484

Other (OTH)

AF:

0.0899

AC:

186

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

650

1301

1951

2602

3252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.0224

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-AACACACACACACAC

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