rs145983470

Positions:

chr11-126001826-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001378964.1(CDON):c.2051C>G(p.Thr684Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00767 in 1,607,342 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 62 hom. )

Consequence

CDON
NM_001378964.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.22

Variant links:

Genes affected

CDON (HGNC:17104): (cell adhesion associated, oncogene regulated) This gene encodes a cell surface receptor that is a member of the immunoglobulin superfamily. The encoded protein contains three fibronectin type III domains and five immunoglobulin-like C2-type domains. This protein is a member of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells and positively regulates myogenesis. [provided by RefSeq, Aug 2011]

CDON links:

CDON (HGNC:):

CDON links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008403778).

BP6

Variant 11-126001826-G-C is Benign according to our data. Variant chr11-126001826-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 303504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-126001826-G-C is described in Lovd as [Likely_pathogenic].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00605 (921/152252) while in subpopulation NFE AF= 0.00813 (553/68022). AF 95% confidence interval is 0.00757. There are 4 homozygotes in gnomad4. There are 476 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 921 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDON	NM_001378964.1 linkuse as main transcript	c.2051C>G	p.Thr684Ser	missense_variant	11/20	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6 linkuse as main transcript	c.2051C>G	p.Thr684Ser	missense_variant	11/20	1	NM_001378964.1	ENSP00000432901.2		Q4KMG0-2E9PN78

Frequencies

GnomAD3 genomes

AF:

0.00605

AC:

921

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0177

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00813

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00693

AC:

1741

AN:

251240

Hom.:

AF XY:

0.00702

AC XY:

953

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00225

Gnomad ASJ exome

AF:

0.0133

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00294

Gnomad FIN exome

AF:

0.0191

Gnomad NFE exome

AF:

0.00840

Gnomad OTH exome

AF:

0.00799

GnomAD4 exome

AF:

0.00784

AC:

11401

AN:

1455090

Hom.:

Cov.:

AF XY:

0.00775

AC XY:

5616

AN XY:

724356

show subpopulations

Gnomad4 AFR exome

AF:

0.000988

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00299

Gnomad4 FIN exome

AF:

0.0207

Gnomad4 NFE exome

AF:

0.00828

Gnomad4 OTH exome

AF:

0.00696

GnomAD4 genome

AF:

0.00605

AC:

921

AN:

152252

Hom.:

Cov.:

AF XY:

0.00640

AC XY:

476

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.0177

Gnomad4 NFE

AF:

0.00813

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00866

Hom.:

Bravo

AF:

0.00496

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00273

AC:

ESP6500EA

AF:

0.00884

AC:

ExAC

AF:

0.00682

AC:

828

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00736

EpiControl

AF:

0.00765

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 09, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	CDON: BP4, BS2 -

Holoprosencephaly 11

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

CDON-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 06, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;.;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.56

T;T;T

MetaRNN

Benign

0.0084

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.7

L;.;L

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.85

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.043

D;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.44

B;B;P

Vest4

0.14

MutPred

0.19

Loss of methylation at K682 (P = 0.0823);.;Loss of methylation at K682 (P = 0.0823);

MVP

0.79

MPC

0.093

ClinPred

0.014

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.20

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