5-11544486-C-T

Variant names:

• chr5-11544486-C-T
• rs2561622
• NM_001332.4:c.287+20458G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001332.4(CTNND2):​c.287+20458G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,114 control chromosomes in the GnomAD database, including 33,690 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 0.66 (33690 hom., cov: 33)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 3 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNND2	NM_001332.4	c.287+20458G>A		intron_variant	Intron 3 of 21	ENST00000304623.13	NP_001323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNND2	ENST00000304623.13	c.287+20458G>A		intron_variant	Intron 3 of 21	1	NM_001332.4	ENSP00000307134.8

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100925 AN: 151996 Hom.: 33667 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.664 AC: 101001 AN: 152114 Hom.: 33690 Cov.: 33 AF XY: 0.668 AC XY: 49657 AN XY: 74362

African (AFR) AF: 0.643 AC: 26664 AN: 41474

American (AMR) AF: 0.599 AC: 9160 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2387 AN: 3466

East Asian (EAS) AF: 0.600 AC: 3103 AN: 5174

South Asian (SAS) AF: 0.670 AC: 3228 AN: 4816

European-Finnish (FIN) AF: 0.771 AC: 8157 AN: 10584

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45932 AN: 67988

Other (OTH) AF: 0.670 AC: 1414 AN: 2112

Alfa AF: 0.675 Hom.: 12610

Bravo AF: 0.651

Asia WGS AF: 0.622 AC: 2161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.068
DANN	Benign	0.45
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2561622; hg19: chr5-11544598;