rs200234049

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_001797.4(CDH11):c.1247C>T(p.Pro416Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000379 in 1,611,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P416P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

CDH11
NM_001797.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.46

Publications

3 publications found

Variant links:

Genes affected

CDH11 (HGNC:1750): (cadherin 11) This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. Expression of this particular cadherin in osteoblastic cell lines, and its upregulation during differentiation, suggests a specific function in bone development and maintenance. [provided by RefSeq, Jul 2008]

CDH11 Gene-Disease associations (from GenCC):

Elsahy-Waters syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
Teebi hypertelorism syndrome 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

CDH11 links:

ENSG00000278893 (HGNC:):

ENSG00000278893 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0229325).

BP6

Variant 16-64982054-G-A is Benign according to our data. Variant chr16-64982054-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 254107.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000046 (7/152048) while in subpopulation AMR AF = 0.000458 (7/15276). AF 95% confidence interval is 0.000215. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001797.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDH11	NM_001797.4	MANE Select	c.1247C>T	p.Pro416Leu	missense	Exon 8 of 13	NP_001788.2
CDH11	NM_001308392.2		c.1247C>T	p.Pro416Leu	missense	Exon 8 of 14	NP_001295321.1	P55287-2
CDH11	NM_001330576.2		c.869C>T	p.Pro290Leu	missense	Exon 7 of 12	NP_001317505.1	H3BUU9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDH11	ENST00000268603.9	TSL:1 MANE Select	c.1247C>T	p.Pro416Leu	missense	Exon 8 of 13	ENSP00000268603.4	P55287-1
CDH11	ENST00000394156.7	TSL:1	c.1247C>T	p.Pro416Leu	missense	Exon 8 of 14	ENSP00000377711.3	P55287-2
CDH11	ENST00000566827.5	TSL:2	c.869C>T	p.Pro290Leu	missense	Exon 7 of 12	ENSP00000457812.1	H3BUU9

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000133

AC:

AN:

248748

AF XY:

0.0000893

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000843

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1459146

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

725666

show subpopulations

African (AFR)

AF:

0.0000599

AC:

AN:

33406

American (AMR)

AF:

0.000808

AC:

AN:

44536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25850

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

85926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53290

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00000991

AC:

AN:

1110488

Other (OTH)

AF:

0.0000332

AC:

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.0000460

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.000458

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

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:

0.0000147

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Oromandibular-limb hypogenesis spectrum (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

Eigen

Benign

-0.014

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.021

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

6.5

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.23

Sift

Benign

0.16

Sift4G

Benign

0.091

Polyphen

0.95

Vest4

0.44

MVP

0.41

MPC

0.47

ClinPred

0.22

GERP RS

4.8

Varity_R

0.13

gMVP

0.48

Mutation Taster

=63/37

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over