rs6884431

Variant names:

• chr5-11111659-A-G
• rs6884431
• NM_001332.4:c.2278-616T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 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.2278-616T>C		intron	N/A	NP_001323.1
	CTNND2	NM_001288715.1		c.2005-616T>C		intron	N/A	NP_001275644.1
	CTNND2	NM_001364128.2		c.1267-616T>C		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.2278-616T>C		intron	N/A	ENSP00000307134.8
	CTNND2	ENST00000511377.5	TSL:1	c.2005-616T>C		intron	N/A	ENSP00000426510.1
	CTNND2	ENST00000513588.5	TSL:1	n.1540-616T>C		intron	N/A	ENSP00000421093.1

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

African (AFR) AF: 0.346 AC: 14371 AN: 41478

American (AMR) AF: 0.444 AC: 6791 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3464

East Asian (EAS) AF: 0.611 AC: 3145 AN: 5150

South Asian (SAS) AF: 0.489 AC: 2345 AN: 4798

European-Finnish (FIN) AF: 0.482 AC: 5083 AN: 10540

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25025 AN: 67938

Other (OTH) AF: 0.390 AC: 823 AN: 2108

Alfa AF: 0.373 Hom.: 29605

Bravo AF: 0.386

Asia WGS AF: 0.542 AC: 1881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.42
PhyloP100		-0.24
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: rs6884431; hg19: chr5-11111771;