Variant rs1041985 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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 links:

ENSG00000227279 (HGNC:):

ENSG00000227279 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1253751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-27963423-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CDH2	NM_001792.5 linkuse as main transcript	c.2448C>T	p.Ala816Ala	synonymous_variant	15/16	ENST00000269141.8	NP_001783.2	P19022-1A0A024RC42
CDH2	NM_001308176.2 linkuse as main transcript	c.2355C>T	p.Ala785Ala	synonymous_variant	14/15		NP_001295105.1	P19022-2
CDH2	XM_017025514.3 linkuse as main transcript	c.2448C>T	p.Ala816Ala	synonymous_variant	15/16		XP_016881003.1
CDH2	XM_011525788.1 linkuse as main transcript	c.2193C>T	p.Ala731Ala	synonymous_variant	15/16		XP_011524090.1	C9J126

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH2	ENST00000269141.8 linkuse as main transcript	c.2448C>T	p.Ala816Ala	synonymous_variant	15/16	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

GnomAD3 exomes

AF:

0.342

AC:

85845

AN:

251212

Hom.:

15458

AF XY:

0.340

AC XY:

46221

AN XY:

135760

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 SAS exome

AF:

0.368

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

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.461

Gnomad4 ASJ exome

AF:

0.305

Gnomad4 EAS exome

AF:

0.419

Gnomad4 SAS exome

AF:

0.370

Gnomad4 FIN exome

AF:

0.353

Gnomad4 NFE exome

AF:

0.309

Gnomad4 OTH exome

AF:

0.325

GnomAD4 genome

AF:

0.294

AC:

44635

AN:

151884

Hom.:

7132

Cov.:

AF XY:

0.298

AC XY:

22135

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.406

Gnomad4 ASJ

AF:

0.304

Gnomad4 EAS

AF:

0.430

Gnomad4 SAS

AF:

0.360

Gnomad4 FIN

AF:

0.366

Gnomad4 NFE

AF:

0.315

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.290

Hom.:

4986

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.29

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over