NM_001332.4:c.287+17006G>A

Variant names:

• chr5-11547938-C-T
• rs11750073
• NM_001332.4:c.287+17006G>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+17006G>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 152,106 control chromosomes in the GnomAD database, including 2,666 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 (2666 hom., cov: 33)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNND2	NM_001332.4	c.287+17006G>A		intron_variant	Intron 3 of 21	ENST00000304623.13	NP_001323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNND2	ENST00000304623.13	c.287+17006G>A		intron_variant	Intron 3 of 21	1	NM_001332.4	ENSP00000307134.8

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26143 AN: 151988 Hom.: 2665 Cov.: 33

Gnomad AFR AF: 0.0921

Gnomad AMI AF: 0.0716

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.172 AC: 26156 AN: 152106 Hom.: 2666 Cov.: 33 AF XY: 0.173 AC XY: 12881 AN XY: 74340

African (AFR) AF: 0.0919 AC: 3814 AN: 41512

American (AMR) AF: 0.288 AC: 4398 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 560 AN: 3466

East Asian (EAS) AF: 0.284 AC: 1464 AN: 5150

South Asian (SAS) AF: 0.184 AC: 886 AN: 4826

European-Finnish (FIN) AF: 0.167 AC: 1768 AN: 10566

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12791 AN: 67984

Other (OTH) AF: 0.181 AC: 384 AN: 2116

Alfa AF: 0.183 Hom.: 8427

Bravo AF: 0.178

Asia WGS AF: 0.236 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.82
PhyloP100		-0.053
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: rs11750073; hg19: chr5-11548050;