5-11386094-G-A

Variant names:

• chr5-11386094-G-A
• rs1479617
• NM_001332.4:c.613-865C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001332.4(CTNND2):​c.613-865C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,114 control chromosomes in the GnomAD database, including 13,110 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 0.41 (13107 hom., cov: 32)
  • Exomes 𝑓: 0.54 (3 hom.)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 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.613-865C>T		intron	N/A	NP_001323.1
	CTNND2	NM_001288715.1		c.340-865C>T		intron	N/A	NP_001275644.1
	CTNND2	NM_001364128.2		c.167-21204C>T		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.613-865C>T		intron	N/A	ENSP00000307134.8
	CTNND2	ENST00000511377.5	TSL:1	c.340-865C>T		intron	N/A	ENSP00000426510.1
	CTNND2	ENST00000513588.5	TSL:1	n.440-21204C>T		intron	N/A	ENSP00000421093.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62667 AN: 151968 Hom.: 13100 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.536 AC: 15 AN: 28 Hom.: 3 AF XY: 0.611 AC XY: 11 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.300 AC: 3 AN: 10

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.625 AC: 10 AN: 16

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.412 AC: 62708 AN: 152086 Hom.: 13107 Cov.: 32 AF XY: 0.415 AC XY: 30859 AN XY: 74352

African (AFR) AF: 0.351 AC: 14553 AN: 41484

American (AMR) AF: 0.444 AC: 6793 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1494 AN: 5174

South Asian (SAS) AF: 0.421 AC: 2026 AN: 4814

European-Finnish (FIN) AF: 0.460 AC: 4864 AN: 10574

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29731 AN: 67970

Other (OTH) AF: 0.415 AC: 874 AN: 2108

Alfa AF: 0.422 Hom.: 21356

Bravo AF: 0.408

Asia WGS AF: 0.401 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.81
PhyloP100		2.5
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: rs1479617; hg19: chr5-11386206;