dbSNP rs757142171: CDH11:p.Arg32Leu (chr16-65004775-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001797.4(CDH11):c.95G>T(p.Arg32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R32Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CDH11
NM_001797.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.677

Publications

5 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
Teebi hypertelorism syndrome 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

CDH11 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11225477).

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
CDH11	NM_001797.4	MANE Select	c.95G>T	p.Arg32Leu	missense	Exon 3 of 13	NP_001788.2
CDH11	NM_001308392.2		c.95G>T	p.Arg32Leu	missense	Exon 3 of 14	NP_001295321.1
CDH11	NM_001330576.2		c.-150-5919G>T		intron	N/A	NP_001317505.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CDH11	ENST00000268603.9	TSL:1 MANE Select	c.95G>T	p.Arg32Leu	missense	Exon 3 of 13	ENSP00000268603.4
CDH11	ENST00000394156.7	TSL:1	c.95G>T	p.Arg32Leu	missense	Exon 3 of 14	ENSP00000377711.3
CDH11	ENST00000567934.5	TSL:2	c.95G>T	p.Arg32Leu	missense	Exon 3 of 6	ENSP00000455779.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

211222

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1439358

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714544

African (AFR)

AF:

0.00

AC:

AN:

32792

American (AMR)

AF:

0.00

AC:

AN:

42444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25736

East Asian (EAS)

AF:

0.00

AC:

AN:

38252

South Asian (SAS)

AF:

0.00

AC:

AN:

84650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5518

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099414

Other (OTH)

AF:

0.00

AC:

AN:

59354

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.10

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.77

M_CAP

Benign

0.018

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

0.68

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.2

REVEL

Benign

0.058

Sift

Benign

0.17

Sift4G

Benign

0.12

Polyphen

0.28

Vest4

0.43

MutPred

0.40

Gain of sheet (P = 0.0043)

MVP

0.59

MPC

1.0

ClinPred

0.20

GERP RS

2.7

Varity_R

0.061

gMVP

0.36

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over