rs32609

Variant names:

• chr5-11489403-T-C
• rs32609
• NM_001332.4:c.287+75541A>G

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+75541A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,080 control chromosomes in the GnomAD database, including 5,980 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 0.27 (5980 hom., cov: 33)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNND2	NM_001332.4	c.287+75541A>G		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+75541A>G		intron_variant	Intron 3 of 21	1	NM_001332.4	ENSP00000307134.8

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41497 AN: 151964 Hom.: 5975 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.273 AC: 41525 AN: 152080 Hom.: 5980 Cov.: 33 AF XY: 0.282 AC XY: 20997 AN XY: 74344

African (AFR) AF: 0.199 AC: 8271 AN: 41492

American (AMR) AF: 0.307 AC: 4683 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3470

East Asian (EAS) AF: 0.181 AC: 938 AN: 5174

South Asian (SAS) AF: 0.399 AC: 1920 AN: 4814

European-Finnish (FIN) AF: 0.425 AC: 4493 AN: 10562

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19462 AN: 67974

Other (OTH) AF: 0.254 AC: 537 AN: 2114

Alfa AF: 0.271 Hom.: 943

Bravo AF: 0.259

Asia WGS AF: 0.267 AC: 928 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.57
DANN	Benign	0.76
PhyloP100		-0.45
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: rs32609; hg19: chr5-11489515;