5-11298111-T-C

Variant names:

• chr5-11298111-T-C
• rs2530215
• NM_001332.4:c.1628+48261A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001332.4(CTNND2):​c.1628+48261A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,972 control chromosomes in the GnomAD database, including 17,985 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 0.48 (17985 hom., cov: 32)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 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.1628+48261A>G		intron	N/A	NP_001323.1
	CTNND2	NM_001288715.1		c.1355+48261A>G		intron	N/A	NP_001275644.1
	CTNND2	NM_001364128.2		c.617+48261A>G		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.1628+48261A>G		intron	N/A	ENSP00000307134.8
	CTNND2	ENST00000511377.5	TSL:1	c.1355+48261A>G		intron	N/A	ENSP00000426510.1
	CTNND2	ENST00000513588.5	TSL:1	n.890+48261A>G		intron	N/A	ENSP00000421093.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73220 AN: 151854 Hom.: 17942 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.483 AC: 73331 AN: 151972 Hom.: 17985 Cov.: 32 AF XY: 0.477 AC XY: 35442 AN XY: 74286

African (AFR) AF: 0.545 AC: 22571 AN: 41408

American (AMR) AF: 0.466 AC: 7119 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1806 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1215 AN: 5162

South Asian (SAS) AF: 0.347 AC: 1671 AN: 4820

European-Finnish (FIN) AF: 0.480 AC: 5067 AN: 10564

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.477 AC: 32419 AN: 67962

Other (OTH) AF: 0.467 AC: 986 AN: 2112

Alfa AF: 0.474 Hom.: 71987

Bravo AF: 0.484

Asia WGS AF: 0.324 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		0.0030
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: rs2530215; hg19: chr5-11298223;