Genetic Variant NM_001332.4:c.1976-7077C>A (chr5-11166836-G-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.1976-7077C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,840 control chromosomes in the GnomAD database, including 12,258 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 0.40 ( 12258 hom., cov: 31)

Consequence

CTNND2
NM_001332.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0660

Publications

11 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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNND2	NM_001332.4 link	c.1976-7077C>A		intron_variant	Intron 11 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.1976-7077C>A		intron_variant	Intron 11 of 21	1	NM_001332.4	ENSP00000307134.8		Q9UQB3-1

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60006

AN:

151722

Hom.:

12246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.406

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.728

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.405

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

GnomAD4 genome

AF:

0.396

AC:

60054

AN:

151840

Hom.:

12258

Cov.:

AF XY:

0.399

AC XY:

29633

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.405

AC:

16775

AN:

41396

American (AMR)

AF:

0.334

AC:

5099

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1372

AN:

3470

East Asian (EAS)

AF:

0.729

AC:

3767

AN:

5168

South Asian (SAS)

AF:

0.353

AC:

1693

AN:

4796

European-Finnish (FIN)

AF:

0.421

AC:

4430

AN:

10534

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.376

AC:

25553

AN:

67896

Other (OTH)

AF:

0.406

AC:

855

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1826

3652

5477

7303

9129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.377

Hom.:

15538

Bravo

AF:

0.396

Asia WGS

AF:

0.486

AC:

1687

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.7

(source)

DANN

Benign

0.36

PhyloP100

0.066

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