rs2276061

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.3549C>T(p.Val1183Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,642 control chromosomes in the GnomAD database, including 75,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5470 hom., cov: 33)

Exomes 𝑓: 0.31 ( 70210 hom. )

Consequence

CDON
NM_001378964.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0530

Publications

24 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 11-125961806-G-A is Benign according to our data. Variant chr11-125961806-G-A is described in ClinVar as Benign. ClinVar VariationId is 260797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.053 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1 link	c.3549C>T	p.Val1183Val	synonymous_variant	Exon 19 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.3549C>T	p.Val1183Val	synonymous_variant	Exon 19 of 20	1	NM_001378964.1	ENSP00000432901.2		Q4KMG0-2E9PN78

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38709

AN:

151982

Hom.:

5468

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.312

Gnomad OTH

AF:

0.251

GnomAD2 exomes

AF:

0.290

AC:

72946

AN:

251112

AF XY:

0.296

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.276

Gnomad ASJ exome

AF:

0.287

Gnomad EAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.317

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.307

AC:

449354

AN:

1461542

Hom.:

70210

Cov.:

AF XY:

0.308

AC XY:

224079

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.116

AC:

3891

AN:

33478

American (AMR)

AF:

0.274

AC:

12264

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

7710

AN:

26136

East Asian (EAS)

AF:

0.279

AC:

11091

AN:

39694

South Asian (SAS)

AF:

0.318

AC:

27440

AN:

86248

European-Finnish (FIN)

AF:

0.311

AC:

16627

AN:

53404

Middle Eastern (MID)

AF:

0.251

AC:

1445

AN:

5768

European-Non Finnish (NFE)

AF:

0.316

AC:

350788

AN:

1111728

Other (OTH)

AF:

0.300

AC:

18098

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

17151

34301

51452

68602

85753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11392

22784

34176

45568

56960

<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:

0.255

AC:

38729

AN:

152100

Hom.:

5470

Cov.:

AF XY:

0.257

AC XY:

19090

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.126

AC:

5228

AN:

41504

American (AMR)

AF:

0.264

AC:

4035

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

1021

AN:

3472

East Asian (EAS)

AF:

0.283

AC:

1459

AN:

5156

South Asian (SAS)

AF:

0.314

AC:

1511

AN:

4808

European-Finnish (FIN)

AF:

0.319

AC:

3371

AN:

10554

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.312

AC:

21224

AN:

68002

Other (OTH)

AF:

0.250

AC:

529

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1421

2842

4262

5683

7104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.291

Hom.:

10507

Bravo

AF:

0.246

Asia WGS

AF:

0.271

AC:

944

AN:

3478

EpiCase

AF:

0.311

EpiControl

AF:

0.314

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Holoprosencephaly 11

Benign:3

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not provided

Benign:2

Dec 23, 2018

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

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.34

(source)

DANN

Benign

0.71

PhyloP100

-0.053

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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