rs1479617

Positions:

• chr5-11386094-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNND2	NM_001332.4	c.613-865C>T		intron_variant		ENST00000304623.13	NP_001323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNND2	ENST00000304623.13	c.613-865C>T		intron_variant		1	NM_001332.4	ENSP00000307134	P1

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

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.625

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

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.415

Alfa AF: 0.421 Hom.: 3071

Bravo AF: 0.408

Asia WGS AF: 0.401 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.81

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: rs1479617; hg19: chr5-11386206;