rs684805

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378964.1(CDON):c.3039C>T(p.Asn1013Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,613,168 control chromosomes in the GnomAD database, including 62,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8310 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54407 hom. )

Consequence

CDON
NM_001378964.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.808

Publications

15 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-125981286-G-A is Benign according to our data. Variant chr11-125981286-G-A is described in ClinVar as Benign. ClinVar VariationId is 260791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.808 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1 link	c.3039C>T	p.Asn1013Asn	synonymous_variant	Exon 17 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.3039C>T	p.Asn1013Asn	synonymous_variant	Exon 17 of 20	1	NM_001378964.1	ENSP00000432901.2		Q4KMG0-2E9PN78

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47789

AN:

151794

Hom.:

8286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.459

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.0795

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.274

GnomAD2 exomes

AF:

0.256

AC:

64369

AN:

251270

AF XY:

0.252

show subpopulations

Gnomad AFR exome

AF:

0.467

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.0800

Gnomad FIN exome

AF:

0.302

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.267

AC:

390628

AN:

1461256

Hom.:

54407

Cov.:

AF XY:

0.265

AC XY:

192620

AN XY:

726976

show subpopulations

African (AFR)

AF:

0.465

AC:

15574

AN:

33466

American (AMR)

AF:

0.210

AC:

9373

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

8740

AN:

26130

East Asian (EAS)

AF:

0.0795

AC:

3155

AN:

39700

South Asian (SAS)

AF:

0.222

AC:

19170

AN:

86250

European-Finnish (FIN)

AF:

0.299

AC:

15965

AN:

53350

Middle Eastern (MID)

AF:

0.230

AC:

1328

AN:

5768

European-Non Finnish (NFE)

AF:

0.271

AC:

301408

AN:

1111492

Other (OTH)

AF:

0.264

AC:

15915

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

16094

32187

48281

64374

80468

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10142

20284

30426

40568

50710

<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:

0.315

AC:

47866

AN:

151912

Hom.:

8310

Cov.:

AF XY:

0.311

AC XY:

23054

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.459

AC:

19015

AN:

41394

American (AMR)

AF:

0.244

AC:

3731

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1169

AN:

3466

East Asian (EAS)

AF:

0.0791

AC:

409

AN:

5168

South Asian (SAS)

AF:

0.211

AC:

1015

AN:

4812

European-Finnish (FIN)

AF:

0.290

AC:

3054

AN:

10544

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.271

AC:

18402

AN:

67956

Other (OTH)

AF:

0.276

AC:

581

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1590

3179

4769

6358

7948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.272

Hom.:

9115

Bravo

AF:

0.317

Asia WGS

AF:

0.206

AC:

716

AN:

3478

EpiCase

AF:

0.256

EpiControl

AF:

0.255

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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 11

Benign:2

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.12

(source)

DANN

Benign

0.52

PhyloP100

-0.81

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