chr5-10981586-A-AACAC

Variant names:

• chr5-10981586-A-AACAC
• rs112742699
• NM_001332.4:c.3417+183_3417+186dupGTGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001332.4(CTNND2):​c.3417+183_3417+186dupGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0064 (8 hom., cov: 20)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-10981586-A-AACAC is Benign according to our data. Variant chr5-10981586-A-AACAC is described in ClinVar as Likely_benign. ClinVar VariationId is 1318181.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00637 (958/150460) while in subpopulation AFR AF = 0.0202 (832/41102). AF 95% confidence interval is 0.0191. There are 8 homozygotes in GnomAd4. There are 463 alleles in the male GnomAd4 subpopulation. Median coverage is 20. This position passed quality control check.
• BS2: High AC in GnomAd4 at 958 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+183_3417+186dupGTGT		intron	N/A	NP_001323.1	Q9UQB3-1
	CTNND2	NM_001288715.1		c.3144+183_3144+186dupGTGT		intron	N/A	NP_001275644.1	Q9UQB3
	CTNND2	NM_001364128.2		c.2481+183_2481+186dupGTGT		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+187insGTGT		intron	N/A	ENSP00000307134.8	Q9UQB3-1
	CTNND2	ENST00000511377.5	TSL:1	c.3144+186_3144+187insGTGT		intron	N/A	ENSP00000426510.1	E7EPC8
	CTNND2	ENST00000513588.5	TSL:1	n.*119+186_*119+187insGTGT		intron	N/A	ENSP00000421093.1	E9PHB5

Frequencies

GnomAD3 genomes AF: 0.00639 AC: 961 AN: 150352 Hom.: 8 Cov.: 20

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00299

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00117

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.000196

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000963

Gnomad OTH AF: 0.00341

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

GnomAD4 genome AF: 0.00637 AC: 958 AN: 150460 Hom.: 8 Cov.: 20 AF XY: 0.00630 AC XY: 463 AN XY: 73434

African (AFR) AF: 0.0202 AC: 832 AN: 41102

American (AMR) AF: 0.00299 AC: 45 AN: 15072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00117 AC: 6 AN: 5122

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4758

European-Finnish (FIN) AF: 0.000196 AC: 2 AN: 10184

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

European-Non Finnish (NFE) AF: 0.000963 AC: 65 AN: 67510

Other (OTH) AF: 0.00337 AC: 7 AN: 2076

Alfa AF: 0.000465 Hom.: 35

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;