chr5-10981608-G-C

Variant names:

• chr5-10981608-G-C
• rs58618024
• NM_001332.4:c.3417+165C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001332.4(CTNND2):​c.3417+165C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,332 control chromosomes in the GnomAD database, including 7,009 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.29 (7009 hom., cov: 32)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.81
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 5-10981608-G-C is Benign according to our data. Variant chr5-10981608-G-C is described in ClinVar as Benign. ClinVar VariationId is 1254980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNND2	NM_001332.4	MANE Select	c.3417+165C>G		intron	N/A	NP_001323.1	Q9UQB3-1
	CTNND2	NM_001288715.1		c.3144+165C>G		intron	N/A	NP_001275644.1	Q9UQB3
	CTNND2	NM_001364128.2		c.2481+165C>G		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+165C>G		intron	N/A	ENSP00000307134.8	Q9UQB3-1
	CTNND2	ENST00000511377.5	TSL:1	c.3144+165C>G		intron	N/A	ENSP00000426510.1	E7EPC8
	CTNND2	ENST00000513588.5	TSL:1	n.*119+165C>G		intron	N/A	ENSP00000421093.1	E9PHB5

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44133 AN: 151220 Hom.: 6986 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.292 AC: 44204 AN: 151332 Hom.: 7009 Cov.: 32 AF XY: 0.289 AC XY: 21361 AN XY: 73960

African (AFR) AF: 0.425 AC: 17430 AN: 40994

American (AMR) AF: 0.225 AC: 3425 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1048 AN: 3412

East Asian (EAS) AF: 0.207 AC: 1064 AN: 5142

South Asian (SAS) AF: 0.128 AC: 615 AN: 4806

European-Finnish (FIN) AF: 0.276 AC: 2911 AN: 10550

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16831 AN: 67884

Other (OTH) AF: 0.280 AC: 589 AN: 2104

Alfa AF: 0.145 Hom.: 262

Bravo AF: 0.299

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.70
DANN	Benign	0.35
PhyloP100		-1.8
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: rs58618024; hg19: chr5-10981720; COSMIC: COSV104394459;