chr5-10973694-G-A

Variant names:

• chr5-10973694-G-A
• NM_001332.4:c.3437C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001332.4(CTNND2):​c.3437C>T​(p.Pro1146Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CTNND2 NM_001332.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.34
• 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

LOC105374654 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20297012).

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.3437C>T	p.Pro1146Leu	missense	Exon 22 of 22	NP_001323.1	Q9UQB3-1
	CTNND2	NM_001288715.1		c.3164C>T	p.Pro1055Leu	missense	Exon 21 of 21	NP_001275644.1	Q9UQB3
	CTNND2	NM_001364128.2		c.2501C>T	p.Pro834Leu	missense	Exon 20 of 20	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.3437C>T	p.Pro1146Leu	missense	Exon 22 of 22	ENSP00000307134.8	Q9UQB3-1
	CTNND2	ENST00000511377.5	TSL:1	c.3164C>T	p.Pro1055Leu	missense	Exon 21 of 21	ENSP00000426510.1	E7EPC8
	CTNND2	ENST00000513588.5	TSL:1	n.*139C>T		non_coding_transcript_exon	Exon 22 of 22	ENSP00000421093.1	E9PHB5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.032
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.0	L
PhyloP100		8.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.26
Sift	Uncertain	0.029	D
Sift4G	Benign	0.48	T
Polyphen		0.012	B
Vest4		0.35
MutPred		0.25		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.47
MPC		0.75
ClinPred		0.91	D
GERP RS		5.9
Varity_R		0.16
gMVP		0.39
Mutation Taster		=59/41	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

hg19: chr5-10973806;