16-64948025-G-A

Position:

chr16-64948025-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001797.4(CDH11):c.1969C>T(p.Arg657Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CDH11
NM_001797.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.42

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.916

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH11	NM_001797.4 linkuse as main transcript	c.1969C>T	p.Arg657Cys	missense_variant	13/13	ENST00000268603.9	NP_001788.2	P55287-1
CDH11	NM_001330576.2 linkuse as main transcript	c.1591C>T	p.Arg531Cys	missense_variant	12/12		NP_001317505.1	H3BUU9
CDH11	XM_047433486.1 linkuse as main transcript	c.1591C>T	p.Arg531Cys	missense_variant	12/12		XP_047289442.1
CDH11	NM_001308392.2 linkuse as main transcript	c.*66C>T		3_prime_UTR_variant	14/14		NP_001295321.1	P55287-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDH11	ENST00000268603.9 linkuse as main transcript	c.1969C>T	p.Arg657Cys	missense_variant	13/13	1	NM_001797.4	ENSP00000268603.4	P55287-1
CDH11	ENST00000394156 linkuse as main transcript	c.*66C>T		3_prime_UTR_variant	14/14	1		ENSP00000377711.3	P55287-2
CDH11	ENST00000566827.5 linkuse as main transcript	c.1591C>T	p.Arg531Cys	missense_variant	12/12	2		ENSP00000457812.1	H3BUU9

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151976

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Teebi hypertelorism syndrome 2

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Diagnostics Centre, Carl Von Ossietzky University Oldenburg

Jan 18, 2024

The variant CDH11:c.1969C>T, p.(Arg657Cys) which is located in the coding exon 13 of the CDH11 gene, results from a cytosine-to-thymine substitution at nucleotide position c.1969. The arginine at protein position 657 is replaced by cysteine, an amino acid with altered properties. This amino acid position is highly conserved in the available vertebrate species. Furthermore, in silico tools a significance deleterious effect in protein structure and function (REVEL= 0.87). The variant is rare in the overall population (allele frequency=0.00001053 in gnomAD, v4.1.0). In summary, this variant is classified as a variant of unclear significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.43

T;T

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.92

D;D

MetaSVM

Pathogenic

0.85

MutationAssessor

Pathogenic

3.2

M;.

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-6.8

D;D

REVEL

Pathogenic

0.87

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.81

MutPred

0.77

Gain of sheet (P = 0.0149);.;

MVP

0.94

MPC

0.87

ClinPred

1.0

GERP RS

4.6

Varity_R

0.73

gMVP

0.94

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