16-64947921-G-C

Position:

chr16-64947921-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The ENST00000268603.9(CDH11):c.2073C>G(p.Ile691Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 1,614,116 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

CDH11
ENST00000268603.9 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.340

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060406327).

BP6

Variant 16-64947921-G-C is Benign according to our data. Variant chr16-64947921-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3025636.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00238 (363/152228) while in subpopulation AFR AF= 0.00801 (333/41550). AF 95% confidence interval is 0.00731. There are 1 homozygotes in gnomad4. There are 166 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CDH11	NM_001797.4 linkuse as main transcript	c.2073C>G	p.Ile691Met	missense_variant	13/13	ENST00000268603.9	NP_001788.2
CDH11	NM_001330576.2 linkuse as main transcript	c.1695C>G	p.Ile565Met	missense_variant	12/12		NP_001317505.1
CDH11	XM_047433486.1 linkuse as main transcript	c.1695C>G	p.Ile565Met	missense_variant	12/12		XP_047289442.1
CDH11	NM_001308392.2 linkuse as main transcript	c.*170C>G		3_prime_UTR_variant	14/14		NP_001295321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH11	ENST00000268603.9 linkuse as main transcript	c.2073C>G	p.Ile691Met	missense_variant	13/13	1	NM_001797.4	ENSP00000268603	P1	P55287-1
CDH11	ENST00000394156.7 linkuse as main transcript	c.*170C>G		3_prime_UTR_variant	14/14	1		ENSP00000377711		P55287-2
CDH11	ENST00000566827.5 linkuse as main transcript	c.1695C>G	p.Ile565Met	missense_variant	12/12	2		ENSP00000457812

Frequencies

GnomAD3 genomes

AF:

0.00238

AC:

362

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00801

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

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:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000529

AC:

133

AN:

251488

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00707

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000439

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000205

AC:

300

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

124

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00699

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.00238

AC:

363

AN:

152228

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

166

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00801

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000445

Hom.:

Bravo

AF:

0.00277

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000708

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CDH11-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

CDH11: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

9.5

DANN

Benign

0.93

DEOGEN2

Benign

0.091

T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.31

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.0060

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.22

Sift

Benign

0.086

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.0030

B;.

Vest4

0.17

MVP

0.58

MPC

0.19

ClinPred

0.0042

GERP RS

2.1

Varity_R

0.064

gMVP

0.58

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