rs1012176

Variant names:

• chr5-11320426-G-T
• rs1012176
• NM_001332.4:c.1628+25946C>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.1628+25946C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,068 control chromosomes in the GnomAD database, including 4,391 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 0.24 (4391 hom., cov: 32)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• Publications: 5 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNND2	NM_001332.4	c.1628+25946C>A		intron_variant	Intron 9 of 21	ENST00000304623.13	NP_001323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNND2	ENST00000304623.13	c.1628+25946C>A		intron_variant	Intron 9 of 21	1	NM_001332.4	ENSP00000307134.8

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36075 AN: 151952 Hom.: 4395 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.237 AC: 36077 AN: 152068 Hom.: 4391 Cov.: 32 AF XY: 0.235 AC XY: 17435 AN XY: 74320

African (AFR) AF: 0.222 AC: 9217 AN: 41476

American (AMR) AF: 0.168 AC: 2563 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3470

East Asian (EAS) AF: 0.375 AC: 1937 AN: 5170

South Asian (SAS) AF: 0.240 AC: 1159 AN: 4822

European-Finnish (FIN) AF: 0.236 AC: 2492 AN: 10562

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17415 AN: 67978

Other (OTH) AF: 0.225 AC: 475 AN: 2114

Alfa AF: 0.249 Hom.: 18896

Bravo AF: 0.233

Asia WGS AF: 0.252 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		0.39
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: rs1012176; hg19: chr5-11320538;