rs6884431

Positions:

• chr5-11111659-A-G
• chr5-11111659-A-T

Variant summary

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

The NM_001332.4(CTNND2):​c.2278-616T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 151,954 control chromosomes in the GnomAD database, including 11,947 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 0.39 (11947 hom., cov: 31)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNND2	NM_001332.4	c.2278-616T>C		intron_variant		ENST00000304623.13	NP_001323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNND2	ENST00000304623.13	c.2278-616T>C		intron_variant		1	NM_001332.4	ENSP00000307134.8

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59352 AN: 151836 Hom.: 11933 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.391 AC: 59401 AN: 151954 Hom.: 11947 Cov.: 31 AF XY: 0.401 AC XY: 29758 AN XY: 74244

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.390

Alfa AF: 0.374 Hom.: 17892

Bravo AF: 0.386

Asia WGS AF: 0.542 AC: 1881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs6884431; hg19: chr5-11111771;