rs35884952

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001378964.1(CDON):c.1671G>A(p.Lys557Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,614,058 control chromosomes in the GnomAD database, including 468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 33 hom., cov: 32)

Exomes 𝑓: 0.023 ( 435 hom. )

Consequence

CDON
NM_001378964.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0280

Publications

3 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.036).

BP6

Variant 11-126005939-C-T is Benign according to our data. Variant chr11-126005939-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.028 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.017 (2586/152212) while in subpopulation NFE AF = 0.0263 (1785/67996). AF 95% confidence interval is 0.0252. There are 33 homozygotes in GnomAd4. There are 1235 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2586 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1 link	c.1671G>A	p.Lys557Lys	synonymous_variant	Exon 9 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.1671G>A	p.Lys557Lys	synonymous_variant	Exon 9 of 20	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2586

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00406

Gnomad AMI

AF:

0.0319

Gnomad AMR

AF:

0.00995

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0326

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0262

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0181

AC:

4544

AN:

251110

AF XY:

0.0182

show subpopulations

Gnomad AFR exome

AF:

0.00400

Gnomad AMR exome

AF:

0.00954

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0315

Gnomad NFE exome

AF:

0.0266

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0229

AC:

33517

AN:

1461846

Hom.:

435

Cov.:

AF XY:

0.0223

AC XY:

16231

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00338

AC:

113

AN:

33480

American (AMR)

AF:

0.00937

AC:

419

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0168

AC:

439

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00636

AC:

549

AN:

86258

European-Finnish (FIN)

AF:

0.0322

AC:

1722

AN:

53420

Middle Eastern (MID)

AF:

0.00641

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0261

AC:

29037

AN:

1111970

Other (OTH)

AF:

0.0199

AC:

1201

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

1964

3928

5891

7855

9819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1074

2148

3222

4296

5370

<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:

0.0170

AC:

2586

AN:

152212

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1235

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00404

AC:

168

AN:

41542

American (AMR)

AF:

0.00994

AC:

152

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00498

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0326

AC:

346

AN:

10608

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0263

AC:

1785

AN:

67996

Other (OTH)

AF:

0.0152

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

122

244

367

489

611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0236

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0234

EpiControl

AF:

0.0247

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 28, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Holoprosencephaly 11

Benign:2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.1

(source)

DANN

Benign

0.46

PhyloP100

0.028

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