rs17183619

chr5-11111141-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001332.4(CTNND2):c.2278-98A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0951 in 1,304,248 control chromosomes in the GnomAD database, including 6,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.077 (591 hom., cov: 32)
  • Exomes 𝑓: 0.097 (5843 hom.)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0110

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-11111141-T-G is Benign according to our data. Variant chr5-11111141-T-G is described in ClinVar as [Benign]. Clinvar id is 1228070.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNND2	NM_001332.4	c.2278-98A>C		intron_variant		ENST00000304623.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNND2	ENST00000304623.13	c.2278-98A>C		intron_variant		1	NM_001332.4	P1

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11757 AN: 152130 Hom.: 587 Cov.: 32

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0829

GnomAD4 exome AF: 0.0974 AC: 112236 AN: 1152000 Hom.: 5843 AF XY: 0.0978 AC XY: 55741 AN XY: 570080

Gnomad4 AFR exome AF: 0.0149

Gnomad4 AMR exome AF: 0.0521

Gnomad4 ASJ exome AF: 0.0712

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.0987

Gnomad4 OTH exome AF: 0.0932

GnomAD4 genome AF: 0.0773 AC: 11770 AN: 152248 Hom.: 591 Cov.: 32 AF XY: 0.0784 AC XY: 5836 AN XY: 74430

Gnomad4 AFR AF: 0.0194

Gnomad4 AMR AF: 0.0672

Gnomad4 ASJ AF: 0.0694

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0872

Alfa AF: 0.0817 Hom.: 87

Bravo AF: 0.0707

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.38
Dann	Benign	0.69

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: rs17183619; hg19: chr5-11111253; COSMIC: COSV104394447;