chr5-10981586-A-AACACACAC

Variant names:

• chr5-10981586-A-AACACACAC
• rs112742699
• NM_001332.4:c.3417+179_3417+186dupGTGTGTGT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001332.4(CTNND2):​c.3417+179_3417+186dupGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0013 (0 hom., cov: 20)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 0 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

LOC105374654 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 198 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNND2	NM_001332.4	MANE Select	c.3417+179_3417+186dupGTGTGTGT		intron	N/A	NP_001323.1	Q9UQB3-1
	CTNND2	NM_001288715.1		c.3144+179_3144+186dupGTGTGTGT		intron	N/A	NP_001275644.1	Q9UQB3
	CTNND2	NM_001364128.2		c.2481+179_2481+186dupGTGTGTGT		intron	N/A	NP_001351057.1	A0A994J5V2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNND2	ENST00000304623.13	TSL:1 MANE Select	c.3417+186_3417+187insGTGTGTGT		intron	N/A	ENSP00000307134.8	Q9UQB3-1
	CTNND2	ENST00000511377.5	TSL:1	c.3144+186_3144+187insGTGTGTGT		intron	N/A	ENSP00000426510.1	E7EPC8
	CTNND2	ENST00000513588.5	TSL:1	n.*119+186_*119+187insGTGTGTGT		intron	N/A	ENSP00000421093.1	E9PHB5

Frequencies

GnomAD3 genomes AF: 0.00132 AC: 199 AN: 150376 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00276

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000797

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.00604

Gnomad SAS AF: 0.000629

Gnomad FIN AF: 0.0000981

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000563

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00132 AC: 198 AN: 150486 Hom.: 0 Cov.: 20 AF XY: 0.00131 AC XY: 96 AN XY: 73446

African (AFR) AF: 0.00275 AC: 113 AN: 41112

American (AMR) AF: 0.000796 AC: 12 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.000291 AC: 1 AN: 3440

East Asian (EAS) AF: 0.00586 AC: 30 AN: 5122

South Asian (SAS) AF: 0.000631 AC: 3 AN: 4758

European-Finnish (FIN) AF: 0.0000981 AC: 1 AN: 10192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000563 AC: 38 AN: 67512

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs112742699; hg19: chr5-10981698;