11-126021374-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378964.1(CDON):c.223G>A(p.Val75Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,613,614 control chromosomes in the GnomAD database, including 262,028 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 Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V75V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.63 ( 31463 hom., cov: 31)

Exomes 𝑓: 0.56 ( 230565 hom. )

Consequence

CDON
NM_001378964.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.22

Publications

39 publications found

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 Gene-Disease associations (from GenCC):

holoprosencephaly 11
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
pituitary stalk interruption syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CDON links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.736624E-7).

BP6

Variant 11-126021374-C-T is Benign according to our data. Variant chr11-126021374-C-T is described in ClinVar as Benign. ClinVar VariationId is 95752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1 link	c.223G>A	p.Val75Ile	missense_variant	Exon 3 of 20	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6 link	c.223G>A	p.Val75Ile	missense_variant	Exon 3 of 20	1	NM_001378964.1	ENSP00000432901.2		Q4KMG0-2E9PN78

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95653

AN:

151916

Hom.:

31412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.814

Gnomad AMI

AF:

0.708

Gnomad AMR

AF:

0.561

Gnomad ASJ

AF:

0.591

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.645

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.572

GnomAD2 exomes

AF:

0.554

AC:

139325

AN:

251292

AF XY:

0.551

show subpopulations

Gnomad AFR exome

AF:

0.820

Gnomad AMR exome

AF:

0.504

Gnomad ASJ exome

AF:

0.612

Gnomad EAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.635

Gnomad NFE exome

AF:

0.556

Gnomad OTH exome

AF:

0.555

GnomAD4 exome

AF:

0.558

AC:

814980

AN:

1461580

Hom.:

230565

Cov.:

AF XY:

0.556

AC XY:

404346

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.825

AC:

27619

AN:

33472

American (AMR)

AF:

0.508

AC:

22736

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.605

AC:

15816

AN:

26134

East Asian (EAS)

AF:

0.303

AC:

12017

AN:

39696

South Asian (SAS)

AF:

0.528

AC:

45505

AN:

86250

European-Finnish (FIN)

AF:

0.628

AC:

33533

AN:

53420

Middle Eastern (MID)

AF:

0.548

AC:

3160

AN:

5768

European-Non Finnish (NFE)

AF:

0.558

AC:

620209

AN:

1111740

Other (OTH)

AF:

0.569

AC:

34385

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

18859

37718

56577

75436

94295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17358

34716

52074

69432

86790

<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:

0.630

AC:

95762

AN:

152034

Hom.:

31463

Cov.:

AF XY:

0.628

AC XY:

46668

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.815

AC:

33786

AN:

41476

American (AMR)

AF:

0.560

AC:

8559

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.591

AC:

2052

AN:

3470

East Asian (EAS)

AF:

0.319

AC:

1648

AN:

5160

South Asian (SAS)

AF:

0.522

AC:

2516

AN:

4822

European-Finnish (FIN)

AF:

0.645

AC:

6803

AN:

10540

Middle Eastern (MID)

AF:

0.627

AC:

183

AN:

292

European-Non Finnish (NFE)

AF:

0.564

AC:

38363

AN:

67972

Other (OTH)

AF:

0.571

AC:

1206

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1708

3416

5123

6831

8539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

760

1520

2280

3040

3800

<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:

0.574

Hom.:

127501

Bravo

AF:

0.628

TwinsUK

AF:

0.552

AC:

2045

ALSPAC

AF:

0.547

AC:

2109

ESP6500AA

AF:

0.802

AC:

3530

ESP6500EA

AF:

0.565

AC:

4857

ExAC

AF:

0.557

AC:

67644

Asia WGS

AF:

0.489

AC:

1699

AN:

3478

EpiCase

AF:

0.559

EpiControl

AF:

0.558

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 03, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Holoprosencephaly 11

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jan 09, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.7

(source)

DANN

Benign

0.20

DEOGEN2

Benign

0.21

T;.;.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.21

T;T;T;T;T

MetaRNN

Benign

9.7e-7

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.65

N;N;.;.;.

PhyloP100

1.2

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.28

N;N;N;N;N

REVEL

Benign

0.058

Sift

Benign

0.79

T;T;T;T;T

Sift4G

Benign

0.62

T;T;.;.;.

Polyphen

0.0010

B;B;B;.;.

Vest4

0.024

MPC

0.081

ClinPred

0.0019

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.046

gMVP

0.22

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over