rs1041985

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001792.5(CDH2):c.2448C>T(p.Ala816Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,612,960 control chromosomes in the GnomAD database, including 83,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A816A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.29 ( 7132 hom., cov: 31)

Exomes 𝑓: 0.32 ( 76257 hom. )

Consequence

CDH2
NM_001792.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.48

Publications

20 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:

ENSG00000227279 (HGNC:40138):

ENSG00000227279 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 18-27963423-G-A is Benign according to our data. Variant chr18-27963423-G-A is described in ClinVar as Benign. ClinVar VariationId is 1253751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH2	NM_001792.5 link	c.2448C>T	p.Ala816Ala	synonymous_variant	Exon 15 of 16	ENST00000269141.8	NP_001783.2	P19022-1A0A024RC42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH2	ENST00000269141.8 link	c.2448C>T	p.Ala816Ala	synonymous_variant	Exon 15 of 16	1	NM_001792.5	ENSP00000269141.3		P19022-1

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44609

AN:

151766

Hom.:

7122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.321

GnomAD2 exomes

AF:

0.342

AC:

85845

AN:

251212

AF XY:

0.340

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.468

Gnomad ASJ exome

AF:

0.303

Gnomad EAS exome

AF:

0.419

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.319

AC:

466246

AN:

1461076

Hom.:

76257

Cov.:

AF XY:

0.321

AC XY:

233129

AN XY:

726854

show subpopulations

African (AFR)

AF:

0.168

AC:

5607

AN:

33474

American (AMR)

AF:

0.461

AC:

20589

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

7970

AN:

26126

East Asian (EAS)

AF:

0.419

AC:

16653

AN:

39698

South Asian (SAS)

AF:

0.370

AC:

31932

AN:

86244

European-Finnish (FIN)

AF:

0.353

AC:

18872

AN:

53412

Middle Eastern (MID)

AF:

0.337

AC:

1935

AN:

5734

European-Non Finnish (NFE)

AF:

0.309

AC:

343086

AN:

1111304

Other (OTH)

AF:

0.325

AC:

19602

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

16436

32871

49307

65742

82178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11318

22636

33954

45272

56590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.294

AC:

44635

AN:

151884

Hom.:

7132

Cov.:

AF XY:

0.298

AC XY:

22135

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.171

AC:

7091

AN:

41408

American (AMR)

AF:

0.406

AC:

6200

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1054

AN:

3470

East Asian (EAS)

AF:

0.430

AC:

2216

AN:

5158

South Asian (SAS)

AF:

0.360

AC:

1730

AN:

4806

European-Finnish (FIN)

AF:

0.366

AC:

3848

AN:

10522

Middle Eastern (MID)

AF:

0.312

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.315

AC:

21432

AN:

67948

Other (OTH)

AF:

0.321

AC:

676

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1572

3145

4717

6290

7862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.291

Hom.:

5523

Bravo

AF:

0.291

Asia WGS

AF:

0.405

AC:

1411

AN:

3478

EpiCase

AF:

0.324

EpiControl

AF:

0.318

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.29

(source)

DANN

Benign

0.76

PhyloP100

-2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over