5-11043805-A-T

Variant names:

• chr5-11043805-A-T
• rs2973488
• NM_001332.4:c.2789-20826T>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.2789-20826T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,126 control chromosomes in the GnomAD database, including 5,684 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 0.19 (5684 hom., cov: 32)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 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.2789-20826T>A		intron	N/A	NP_001323.1
	CTNND2	NM_001288715.1		c.2516-20826T>A		intron	N/A	NP_001275644.1
	CTNND2	NM_001364128.2		c.1853-20826T>A		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.2789-20826T>A		intron	N/A	ENSP00000307134.8
	CTNND2	ENST00000511377.5	TSL:1	c.2516-20826T>A		intron	N/A	ENSP00000426510.1
	CTNND2	ENST00000513588.5	TSL:1	n.2126-20826T>A		intron	N/A	ENSP00000421093.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29326 AN: 152008 Hom.: 5690 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0632

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0455

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.193 AC: 29346 AN: 152126 Hom.: 5684 Cov.: 32 AF XY: 0.196 AC XY: 14574 AN XY: 74392

African (AFR) AF: 0.463 AC: 19183 AN: 41446

American (AMR) AF: 0.113 AC: 1726 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0632 AC: 219 AN: 3466

East Asian (EAS) AF: 0.577 AC: 2982 AN: 5172

South Asian (SAS) AF: 0.235 AC: 1134 AN: 4822

European-Finnish (FIN) AF: 0.0610 AC: 646 AN: 10596

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0455 AC: 3093 AN: 68020

Other (OTH) AF: 0.149 AC: 314 AN: 2112

Alfa AF: 0.120 Hom.: 356

Bravo AF: 0.207

Asia WGS AF: 0.392 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.85
PhyloP100		-0.44
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: rs2973488; hg19: chr5-11043917;