chr11-126019631-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.484G>A(p.Glu162Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 1,613,658 control chromosomes in the GnomAD database, including 7,351 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 (★★).

Frequency

Genomes: 𝑓 0.10 ( 861 hom., cov: 32)

Exomes 𝑓: 0.092 ( 6490 hom. )

Consequence

CDON
NM_001378964.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.75

Publications

26 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=0.0015831888).

BP6

Variant 11-126019631-C-T is Benign according to our data. Variant chr11-126019631-C-T is described in ClinVar as Benign. ClinVar VariationId is 260800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1 link	c.484G>A	p.Glu162Lys	missense_variant	Exon 4 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.484G>A	p.Glu162Lys	missense_variant	Exon 4 of 20	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15774

AN:

151960

Hom.:

858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.0982

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0878

Gnomad OTH

AF:

0.100

GnomAD2 exomes

AF:

0.109

AC:

27308

AN:

251340

AF XY:

0.107

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.0859

Gnomad OTH exome

AF:

0.0992

GnomAD4 exome

AF:

0.0919

AC:

134384

AN:

1461580

Hom.:

6490

Cov.:

AF XY:

0.0923

AC XY:

67077

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.112

AC:

3741

AN:

33474

American (AMR)

AF:

0.141

AC:

6301

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2689

AN:

26136

East Asian (EAS)

AF:

0.123

AC:

4879

AN:

39698

South Asian (SAS)

AF:

0.116

AC:

10003

AN:

86256

European-Finnish (FIN)

AF:

0.125

AC:

6696

AN:

53420

Middle Eastern (MID)

AF:

0.0709

AC:

409

AN:

5768

European-Non Finnish (NFE)

AF:

0.0844

AC:

93778

AN:

1111726

Other (OTH)

AF:

0.0975

AC:

5888

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

6308

12616

18925

25233

31541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3596

7192

10788

14384

17980

<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:

0.104

AC:

15806

AN:

152078

Hom.:

861

Cov.:

AF XY:

0.106

AC XY:

7867

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.114

AC:

4732

AN:

41490

American (AMR)

AF:

0.126

AC:

1923

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0982

AC:

341

AN:

3472

East Asian (EAS)

AF:

0.122

AC:

630

AN:

5162

South Asian (SAS)

AF:

0.122

AC:

586

AN:

4820

European-Finnish (FIN)

AF:

0.127

AC:

1345

AN:

10576

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0878

AC:

5967

AN:

67982

Other (OTH)

AF:

0.104

AC:

220

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

714

1428

2141

2855

3569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.0926

Hom.:

2376

Bravo

AF:

0.103

TwinsUK

AF:

0.0912

AC:

338

ALSPAC

AF:

0.0856

AC:

330

ESP6500AA

AF:

0.124

AC:

545

ESP6500EA

AF:

0.0860

AC:

739

ExAC

AF:

0.106

AC:

12837

Asia WGS

AF:

0.162

AC:

561

AN:

3478

EpiCase

AF:

0.0832

EpiControl

AF:

0.0852

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 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

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.32

T;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.042

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.16

T;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.35

N;N;.

PhyloP100

1.8

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.18

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.31

T;T;.

Polyphen

0.0

B;B;B

Vest4

0.023

MPC

0.11

ClinPred

0.0059

GERP RS

4.0

Varity_R

0.072

gMVP

0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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