rs10038337

Variant names:

• chr5-11512345-G-T
• rs10038337
• NM_001332.4:c.287+52599C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001332.4(CTNND2):​c.287+52599C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,172 control chromosomes in the GnomAD database, including 3,711 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 0.17 (3711 hom., cov: 33)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 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.287+52599C>A		intron	N/A	NP_001323.1
	CTNND2	NM_001288715.1		c.14+52599C>A		intron	N/A	NP_001275644.1
	CTNND2	NM_001364128.2		c.14+52599C>A		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.287+52599C>A		intron	N/A	ENSP00000307134.8
	CTNND2	ENST00000511377.5	TSL:1	c.14+52599C>A		intron	N/A	ENSP00000426510.1
	CTNND2	ENST00000513588.5	TSL:1	n.287+52599C>A		intron	N/A	ENSP00000421093.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26163 AN: 152054 Hom.: 3691 Cov.: 33

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0833

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.0434

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.172 AC: 26227 AN: 152172 Hom.: 3711 Cov.: 33 AF XY: 0.165 AC XY: 12271 AN XY: 74414

African (AFR) AF: 0.391 AC: 16220 AN: 41512

American (AMR) AF: 0.0830 AC: 1268 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 373 AN: 3472

East Asian (EAS) AF: 0.0309 AC: 160 AN: 5178

South Asian (SAS) AF: 0.0476 AC: 229 AN: 4814

European-Finnish (FIN) AF: 0.0434 AC: 461 AN: 10612

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7082 AN: 67986

Other (OTH) AF: 0.144 AC: 305 AN: 2112

Alfa AF: 0.117 Hom.: 2352

Bravo AF: 0.183

Asia WGS AF: 0.0700 AC: 247 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.67
PhyloP100		-0.031
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: rs10038337; hg19: chr5-11512457;