Genetic Variant NM_001332.4:c.1629-15332G>A (chr5-11252155-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001332.4(CTNND2):c.1629-15332G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,044 control chromosomes in the GnomAD database, including 10,809 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10809 hom., cov: 32)

Consequence

CTNND2
NM_001332.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.600

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNND2	NM_001332.4 link	c.1629-15332G>A		intron_variant	Intron 9 of 21	ENST00000304623.13	NP_001323.1	Q9UQB3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNND2	ENST00000304623.13 link	c.1629-15332G>A		intron_variant	Intron 9 of 21	1	NM_001332.4	ENSP00000307134.8		Q9UQB3-1

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

56067

AN:

151924

Hom.:

10782

Cov.:

show subpopulations

Gnomad AFR

AF:

0.464

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.334

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

GnomAD4 genome

AF:

0.369

AC:

56159

AN:

152044

Hom.:

10809

Cov.:

AF XY:

0.366

AC XY:

27207

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.465

AC:

19285

AN:

41462

American (AMR)

AF:

0.313

AC:

4788

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

1368

AN:

3468

East Asian (EAS)

AF:

0.221

AC:

1138

AN:

5160

South Asian (SAS)

AF:

0.254

AC:

1223

AN:

4824

European-Finnish (FIN)

AF:

0.343

AC:

3624

AN:

10560

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.347

AC:

23589

AN:

67978

Other (OTH)

AF:

0.335

AC:

708

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1778

3556

5335

7113

8891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.343

Hom.:

14502

Bravo

AF:

0.371

Asia WGS

AF:

0.282

AC:

981

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

(source)

DANN

Benign

0.45

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over