chr5-11111141-T-G

Variant names:

• chr5-11111141-T-G
• rs17183619
• NM_001332.4:c.2278-98A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001332.4(CTNND2):​c.2278-98A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0951 in 1,304,248 control chromosomes in the GnomAD database, including 6,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (591 hom., cov: 32)
  • Exomes 𝑓: 0.097 (5843 hom.)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0110
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-11111141-T-G is Benign according to our data. Variant chr5-11111141-T-G is described in ClinVar as Benign. ClinVar VariationId is 1228070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 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.2278-98A>C		intron	N/A	NP_001323.1
	CTNND2	NM_001288715.1		c.2005-98A>C		intron	N/A	NP_001275644.1
	CTNND2	NM_001364128.2		c.1267-98A>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.2278-98A>C		intron	N/A	ENSP00000307134.8
	CTNND2	ENST00000511377.5	TSL:1	c.2005-98A>C		intron	N/A	ENSP00000426510.1
	CTNND2	ENST00000513588.5	TSL:1	n.1540-98A>C		intron	N/A	ENSP00000421093.1

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11757 AN: 152130 Hom.: 587 Cov.: 32

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0829

GnomAD4 exome AF: 0.0974 AC: 112236 AN: 1152000 Hom.: 5843 AF XY: 0.0978 AC XY: 55741 AN XY: 570080

African (AFR) AF: 0.0149 AC: 395 AN: 26504

American (AMR) AF: 0.0521 AC: 1498 AN: 28776

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 1367 AN: 19202

East Asian (EAS) AF: 0.122 AC: 4549 AN: 37204

South Asian (SAS) AF: 0.112 AC: 7045 AN: 62846

European-Finnish (FIN) AF: 0.127 AC: 5824 AN: 45710

Middle Eastern (MID) AF: 0.0579 AC: 200 AN: 3452

European-Non Finnish (NFE) AF: 0.0987 AC: 86763 AN: 879006

Other (OTH) AF: 0.0932 AC: 4595 AN: 49300

GnomAD4 genome AF: 0.0773 AC: 11770 AN: 152248 Hom.: 591 Cov.: 32 AF XY: 0.0784 AC XY: 5836 AN XY: 74430

African (AFR) AF: 0.0194 AC: 808 AN: 41562

American (AMR) AF: 0.0672 AC: 1028 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 241 AN: 3472

East Asian (EAS) AF: 0.110 AC: 571 AN: 5176

South Asian (SAS) AF: 0.117 AC: 562 AN: 4822

European-Finnish (FIN) AF: 0.127 AC: 1350 AN: 10594

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6881 AN: 68010

Other (OTH) AF: 0.0872 AC: 184 AN: 2110

Alfa AF: 0.0614 Hom.: 94

Bravo AF: 0.0707

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Aug 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.38
DANN	Benign	0.69
PhyloP100		0.011
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: rs17183619; hg19: chr5-11111253;