dbSNP rs11564386: CDH2:c.172+26846A>G (chr18-28120827-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001792.5(CDH2):c.172+26846A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 152,176 control chromosomes in the GnomAD database, including 184 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 0.045 ( 184 hom., cov: 32)

Consequence

CDH2
NM_001792.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.436

Publications

4 publications found

Variant links:

Genes affected

CDH2 (HGNC:1759): (cadherin 2) This gene encodes a classical cadherin and member of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein is proteolytically processed to generate a calcium-dependent cell adhesion molecule and glycoprotein. This protein plays a role in the establishment of left-right asymmetry, development of the nervous system and the formation of cartilage and bone. [provided by RefSeq, Nov 2015]

CDH2 Gene-Disease associations (from GenCC):

agenesis of corpus callosum, cardiac, ocular, and genital syndrome
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
arrhythmogenic right ventricular dysplasia, familial, 14
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CDH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CDH2	NM_001792.5 link	c.172+26846A>G	intron_variant	Intron 2 of 15	ENST00000269141.8	NP_001783.2	P19022-1A0A024RC42
CDH2	XM_017025514.3 link	c.172+26846A>G	intron_variant	Intron 2 of 15		XP_016881003.1
CDH2	XM_011525788.1 link	c.-84+26846A>G	intron_variant	Intron 2 of 15		XP_011524090.1	C9J126

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH2	ENST00000269141.8 link	c.172+26846A>G		intron_variant	Intron 2 of 15	1	NM_001792.5	ENSP00000269141.3		P19022-1

Frequencies

GnomAD3 genomes

AF:

0.0453

AC:

6881

AN:

152056

Hom.:

184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0569

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.0431

Gnomad SAS

AF:

0.0836

Gnomad FIN

AF:

0.0456

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0396

Gnomad OTH

AF:

0.0416

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

GnomAD4 genome

AF:

0.0452

AC:

6881

AN:

152176

Hom.:

184

Cov.:

AF XY:

0.0452

AC XY:

3364

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0570

AC:

2367

AN:

41542

American (AMR)

AF:

0.0265

AC:

405

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0317

AC:

110

AN:

3468

East Asian (EAS)

AF:

0.0431

AC:

223

AN:

5170

South Asian (SAS)

AF:

0.0822

AC:

397

AN:

4828

European-Finnish (FIN)

AF:

0.0456

AC:

483

AN:

10596

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0396

AC:

2695

AN:

67984

Other (OTH)

AF:

0.0407

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

326

652

979

1305

1631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0409

Hom.:

227

Bravo

AF:

0.0422

Asia WGS

AF:

0.0520

AC:

182

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.32

(source)

DANN

Benign

0.48

PhyloP100

-0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over