dbSNP rs2298574: CDH2:c.1599-428T>C (chr18-27989094-A-G) – 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.1599-428T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 152,266 control chromosomes in the GnomAD database, including 400 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 0.069 ( 400 hom., cov: 32)

Consequence

CDH2
NM_001792.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0820

Publications

6 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=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CDH2	NM_001792.5 link	c.1599-428T>C	intron_variant	Intron 10 of 15	ENST00000269141.8	NP_001783.2	P19022-1A0A024RC42
CDH2	NM_001308176.2 link	c.1506-428T>C	intron_variant	Intron 9 of 14		NP_001295105.1	P19022-2
CDH2	XM_017025514.3 link	c.1599-428T>C	intron_variant	Intron 10 of 15		XP_016881003.1
CDH2	XM_011525788.1 link	c.1344-428T>C	intron_variant	Intron 10 of 15		XP_011524090.1	C9J126

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH2	ENST00000269141.8 link	c.1599-428T>C		intron_variant	Intron 10 of 15	1	NM_001792.5	ENSP00000269141.3		P19022-1

Frequencies

GnomAD3 genomes

AF:

0.0692

AC:

10532

AN:

152146

Hom.:

400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0424

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0387

Gnomad ASJ

AF:

0.0931

Gnomad EAS

AF:

0.0501

Gnomad SAS

AF:

0.0919

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0852

Gnomad OTH

AF:

0.0584

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

GnomAD4 genome

AF:

0.0691

AC:

10523

AN:

152266

Hom.:

400

Cov.:

AF XY:

0.0694

AC XY:

5169

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0423

AC:

1757

AN:

41564

American (AMR)

AF:

0.0386

AC:

591

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0931

AC:

323

AN:

3470

East Asian (EAS)

AF:

0.0502

AC:

260

AN:

5180

South Asian (SAS)

AF:

0.0908

AC:

438

AN:

4826

European-Finnish (FIN)

AF:

0.106

AC:

1122

AN:

10602

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0853

AC:

5798

AN:

68010

Other (OTH)

AF:

0.0573

AC:

121

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

498

995

1493

1990

2488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.0812

Hom.:

1754

Bravo

AF:

0.0636

Asia WGS

AF:

0.0500

AC:

173

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.75

(source)

DANN

Benign

0.68

PhyloP100

-0.082

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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