5-11385039-G-A

Variant names:

• chr5-11385039-G-A
• rs765655737
• NM_001332.4:c.803C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001332.4(CTNND2):​c.803C>T​(p.Pro268Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000034 in 1,177,376 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P268Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: CTNND2 NM_001332.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.15
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNND2	NM_001332.4	MANE Select	c.803C>T	p.Pro268Leu	missense	Exon 7 of 22	NP_001323.1	Q9UQB3-1
	CTNND2	NM_001288715.1		c.530C>T	p.Pro177Leu	missense	Exon 6 of 21	NP_001275644.1	Q9UQB3
	CTNND2	NM_001364128.2		c.167-20149C>T		intron	N/A	NP_001351057.1	A0A994J5V2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNND2	ENST00000304623.13	TSL:1 MANE Select	c.803C>T	p.Pro268Leu	missense	Exon 7 of 22	ENSP00000307134.8	Q9UQB3-1
	CTNND2	ENST00000511377.5	TSL:1	c.530C>T	p.Pro177Leu	missense	Exon 6 of 21	ENSP00000426510.1	E7EPC8
	CTNND2	ENST00000513588.5	TSL:1	n.440-20149C>T		intron	N/A	ENSP00000421093.1	E9PHB5

Frequencies

GnomAD3 genomes AF: 0.00000676 AC: 1 AN: 147980 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000291 AC: 3 AN: 1029396 Hom.: 0 Cov.: 30 AF XY: 0.00000408 AC XY: 2 AN XY: 489670

African (AFR) AF: 0.00 AC: 0 AN: 20718

American (AMR) AF: 0.00 AC: 0 AN: 6362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11334

East Asian (EAS) AF: 0.00 AC: 0 AN: 20254

South Asian (SAS) AF: 0.00 AC: 0 AN: 19326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2602

European-Non Finnish (NFE) AF: 0.00000337 AC: 3 AN: 891170

Other (OTH) AF: 0.00 AC: 0 AN: 39370

GnomAD4 genome AF: 0.00000676 AC: 1 AN: 147980 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72060

African (AFR) AF: 0.00 AC: 0 AN: 40958

American (AMR) AF: 0.00 AC: 0 AN: 14908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.00 AC: 0 AN: 5066

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66504

Other (OTH) AF: 0.00 AC: 0 AN: 2030

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.60	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.1
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.27		Gain of stability (P = 0.047)
MVP		0.91
MPC		2.1
ClinPred		0.98	D
GERP RS		3.5
Varity_R		0.40
gMVP		0.60
Mutation Taster		=67/33	polymorphism

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: rs765655737; hg19: chr5-11385151;