11-125961075-A-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.3662T>A(p.Ile1221Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,613,132 control chromosomes in the GnomAD database, including 403,270 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 42774 hom., cov: 33)

Exomes 𝑓: 0.70 ( 360496 hom. )

Consequence

CDON
NM_001378964.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.447

Publications

29 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=4.3759915E-6).

BP6

Variant 11-125961075-A-T is Benign according to our data. Variant chr11-125961075-A-T is described in ClinVar as Benign. ClinVar VariationId is 260799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1 link	c.3662T>A	p.Ile1221Asn	missense_variant	Exon 20 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.3662T>A	p.Ile1221Asn	missense_variant	Exon 20 of 20	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes

AF:

0.746

AC:

113304

AN:

151982

Hom.:

42730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.840

Gnomad AMI

AF:

0.528

Gnomad AMR

AF:

0.770

Gnomad ASJ

AF:

0.738

Gnomad EAS

AF:

0.923

Gnomad SAS

AF:

0.740

Gnomad FIN

AF:

0.694

Gnomad MID

AF:

0.745

Gnomad NFE

AF:

0.680

Gnomad OTH

AF:

0.744

GnomAD2 exomes

AF:

0.732

AC:

183804

AN:

251040

AF XY:

0.727

show subpopulations

Gnomad AFR exome

AF:

0.844

Gnomad AMR exome

AF:

0.784

Gnomad ASJ exome

AF:

0.728

Gnomad EAS exome

AF:

0.925

Gnomad FIN exome

AF:

0.680

Gnomad NFE exome

AF:

0.682

Gnomad OTH exome

AF:

0.733

GnomAD4 exome

AF:

0.700

AC:

1023018

AN:

1461030

Hom.:

360496

Cov.:

AF XY:

0.700

AC XY:

509011

AN XY:

726806

show subpopulations

African (AFR)

AF:

0.847

AC:

28363

AN:

33474

American (AMR)

AF:

0.780

AC:

34890

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.732

AC:

19123

AN:

26126

East Asian (EAS)

AF:

0.930

AC:

36908

AN:

39698

South Asian (SAS)

AF:

0.722

AC:

62236

AN:

86202

European-Finnish (FIN)

AF:

0.679

AC:

36276

AN:

53410

Middle Eastern (MID)

AF:

0.714

AC:

4121

AN:

5768

European-Non Finnish (NFE)

AF:

0.682

AC:

757535

AN:

1111266

Other (OTH)

AF:

0.722

AC:

43566

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

15654

31308

46961

62615

78269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19528

39056

58584

78112

97640

<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:

0.746

AC:

113406

AN:

152102

Hom.:

42774

Cov.:

AF XY:

0.748

AC XY:

55582

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.841

AC:

34909

AN:

41526

American (AMR)

AF:

0.770

AC:

11779

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.738

AC:

2560

AN:

3468

East Asian (EAS)

AF:

0.923

AC:

4773

AN:

5170

South Asian (SAS)

AF:

0.739

AC:

3534

AN:

4784

European-Finnish (FIN)

AF:

0.694

AC:

7341

AN:

10572

Middle Eastern (MID)

AF:

0.747

AC:

218

AN:

292

European-Non Finnish (NFE)

AF:

0.680

AC:

46247

AN:

67970

Other (OTH)

AF:

0.741

AC:

1566

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1490

2980

4471

5961

7451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<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:

0.698

Hom.:

12090

Bravo

AF:

0.759

TwinsUK

AF:

0.675

AC:

2502

ALSPAC

AF:

0.684

AC:

2637

ESP6500AA

AF:

0.826

AC:

3635

ESP6500EA

AF:

0.681

AC:

5855

ExAC

AF:

0.731

AC:

88720

Asia WGS

AF:

0.802

AC:

2788

AN:

3478

EpiCase

AF:

0.695

EpiControl

AF:

0.692

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Holoprosencephaly 11

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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. -

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Holoprosencephaly 1

Benign:1

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.7

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.20

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.39

T;T;T

MetaRNN

Benign

0.0000044

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.0

N;.;.

PhyloP100

0.45

PrimateAI

Benign

0.36

PROVEAN

Benign

2.5

N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.16

MPC

0.17

ClinPred

0.0014

GERP RS

4.3

Varity_R

0.027

gMVP

0.071

Mutation Taster

=98/2

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