5-11218376-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001332.4(CTNND2):c.1761+18315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,896 control chromosomes in the GnomAD database, including 20,487 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 0.52 (20487 hom., cov: 32)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.00

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNND2	NM_001332.4	c.1761+18315G>A		intron_variant		ENST00000304623.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNND2	ENST00000304623.13	c.1761+18315G>A		intron_variant		1	NM_001332.4	P1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78391 AN: 151778 Hom.: 20497 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.516 AC: 78398 AN: 151896 Hom.: 20487 Cov.: 32 AF XY: 0.519 AC XY: 38506 AN XY: 74240

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.532

Alfa AF: 0.517 Hom.: 31414

Bravo AF: 0.519

Asia WGS AF: 0.599 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.017
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs27520; hg19: chr5-11218488;