chr5-11352989-A-G

Variant names:

• chr5-11352989-A-G
• rs10513097
• NM_001332.4:c.1373-6362T>C

Variant summary

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

The NM_001332.4(CTNND2):​c.1373-6362T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,488 control chromosomes in the GnomAD database, including 3,856 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 0.22 (3856 hom., cov: 31)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001332.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNND2	NM_001332.4	MANE Select	c.1373-6362T>C		intron	N/A	NP_001323.1
	CTNND2	NM_001288715.1		c.1100-6362T>C		intron	N/A	NP_001275644.1
	CTNND2	NM_001364128.2		c.362-6362T>C		intron	N/A	NP_001351057.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNND2	ENST00000304623.13	TSL:1 MANE Select	c.1373-6362T>C		intron	N/A	ENSP00000307134.8
	CTNND2	ENST00000511377.5	TSL:1	c.1100-6362T>C		intron	N/A	ENSP00000426510.1
	CTNND2	ENST00000513588.5	TSL:1	n.635-6362T>C		intron	N/A	ENSP00000421093.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 32939 AN: 151398 Hom.: 3847 Cov.: 31

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.218 AC: 32964 AN: 151488 Hom.: 3856 Cov.: 31 AF XY: 0.224 AC XY: 16582 AN XY: 73946

African (AFR) AF: 0.178 AC: 7357 AN: 41276

American (AMR) AF: 0.277 AC: 4210 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1150 AN: 3466

East Asian (EAS) AF: 0.184 AC: 951 AN: 5158

South Asian (SAS) AF: 0.303 AC: 1454 AN: 4804

European-Finnish (FIN) AF: 0.323 AC: 3344 AN: 10368

Middle Eastern (MID) AF: 0.262 AC: 76 AN: 290

European-Non Finnish (NFE) AF: 0.202 AC: 13699 AN: 67894

Other (OTH) AF: 0.240 AC: 503 AN: 2100

Alfa AF: 0.219 Hom.: 2603

Bravo AF: 0.212

Asia WGS AF: 0.268 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.85
DANN	Benign	0.34
PhyloP100		-0.13
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: rs10513097; hg19: chr5-11353101;