rs373341715

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001794.5(CDH4):c.2554G>A(p.Ala852Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000077 in 1,598,232 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

CDH4
NM_001794.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86

Publications

1 publications found

Variant links:

Genes affected

CDH4 (HGNC:1763): (cadherin 4) This gene is a classical cadherin from the cadherin superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Based on studies in chicken and mouse, this cadherin is thought to play an important role during brain segmentation and neuronal outgrowth. In addition, a role in kidney and muscle development is indicated. Of particular interest are studies showing stable cis-heterodimers of cadherins 2 and 4 in cotransfected cell lines. Previously thought to interact in an exclusively homophilic manner, this is the first evidence of cadherin heterodimerization. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

CDH4 Gene-Disease associations (from GenCC):

multiple congenital anomalies/dysmorphic syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CDH4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH4	NM_001794.5 link	c.2554G>A	p.Ala852Thr	missense_variant	Exon 16 of 16	ENST00000614565.5	NP_001785.2	P55283-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDH4	ENST00000614565.5 link	c.2554G>A	p.Ala852Thr	missense_variant	Exon 16 of 16	1	NM_001794.5	ENSP00000484928.1	P55283-1
CDH4	ENST00000543233.2 link	c.2332G>A	p.Ala778Thr	missense_variant	Exon 15 of 15	2		ENSP00000443301.1	P55283-2
CDH4	ENST00000611855.4 link	c.2272G>A	p.Ala758Thr	missense_variant	Exon 15 of 15	5		ENSP00000480844.1	A0A087WX99

Frequencies

GnomAD3 genomes

AF:

0.0000989

AC:

AN:

151656

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000507

AC:

AN:

236570

AF XY:

0.0000545

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000313

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000930

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000747

AC:

108

AN:

1446576

Hom.:

Cov.:

AF XY:

0.0000681

AC XY:

AN XY:

719176

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32748

American (AMR)

AF:

0.0000467

AC:

AN:

42870

Ashkenazi Jewish (ASJ)

AF:

0.0000392

AC:

AN:

25530

East Asian (EAS)

AF:

0.00

AC:

AN:

38062

South Asian (SAS)

AF:

0.00

AC:

AN:

84044

European-Finnish (FIN)

AF:

0.0000576

AC:

AN:

52108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000841

AC:

AN:

1105690

Other (OTH)

AF:

0.000134

AC:

AN:

59810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000989

AC:

AN:

151656

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74030

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41264

American (AMR)

AF:

0.00

AC:

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5046

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.0000946

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000216

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000742

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Simplified gyral pattern

Uncertain:1

Sep 01, 2017

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

this variant was indentified in an individual with malformations of cortical development -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.;.

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.090

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.50

D;D;D

MetaSVM

Uncertain

0.062

MutationAssessor

Uncertain

2.7

M;.;.

PhyloP100

7.9

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.6

.;.;D

REVEL

Uncertain

0.52

Sift

Benign

0.077

.;.;T

Sift4G

Uncertain

0.057

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.31

MVP

0.86

ClinPred

0.79

GERP RS

3.5

Varity_R

0.38

gMVP

0.42

Mutation Taster

=74/26

polymorphism

(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