11-126006007-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.1603G>A(p.Ala535Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,614,058 control chromosomes in the GnomAD database, including 266 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 0.021 ( 128 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 138 hom. )

Consequence

CDON
NM_001378964.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.648

Publications

6 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: Illumina, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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=0.0018728971).

BP6

Variant 11-126006007-C-T is Benign according to our data. Variant chr11-126006007-C-T is described in ClinVar as Benign. ClinVar VariationId is 303516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378964.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDON	NM_001378964.1	MANE Select	c.1603G>A	p.Ala535Thr	missense	Exon 9 of 20	NP_001365893.1	Q4KMG0-2
CDON	NM_001243597.3		c.1603G>A	p.Ala535Thr	missense	Exon 9 of 20	NP_001230526.1
CDON	NM_001441161.1		c.1603G>A	p.Ala535Thr	missense	Exon 9 of 20	NP_001428090.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDON	ENST00000531738.6	TSL:1 MANE Select	c.1603G>A	p.Ala535Thr	missense	Exon 9 of 20	ENSP00000432901.2	Q4KMG0-2
CDON	ENST00000392693.7	TSL:1	c.1603G>A	p.Ala535Thr	missense	Exon 9 of 20	ENSP00000376458.3	Q4KMG0-1
CDON	ENST00000263577.11	TSL:1	c.1603G>A	p.Ala535Thr	missense	Exon 9 of 20	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3255

AN:

152116

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0752

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00596

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0125

GnomAD2 exomes

AF:

0.00564

AC:

1411

AN:

250116

AF XY:

0.00424

show subpopulations

Gnomad AFR exome

AF:

0.0786

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.000998

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00227

AC:

3323

AN:

1461824

Hom.:

138

Cov.:

AF XY:

0.00194

AC XY:

1414

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.0809

AC:

2707

AN:

33474

American (AMR)

AF:

0.00344

AC:

154

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000995

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000128

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00468

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000138

AC:

153

AN:

1111982

Other (OTH)

AF:

0.00406

AC:

245

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

174

349

523

698

872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<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:

0.0214

AC:

3262

AN:

152234

Hom.:

128

Cov.:

AF XY:

0.0205

AC XY:

1525

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0751

AC:

3120

AN:

41522

American (AMR)

AF:

0.00595

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68032

Other (OTH)

AF:

0.0123

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

150

300

449

599

749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00963

Hom.:

Bravo

AF:

0.0237

ESP6500AA

AF:

0.0768

AC:

338

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00710

AC:

862

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Holoprosencephaly 11 (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.0080

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.23

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.085

PhyloP100

-0.65

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.33

REVEL

Benign

0.032

Sift

Benign

0.50

Sift4G

Benign

0.80

Polyphen

0.0020

Vest4

0.038

MVP

0.62

MPC

0.093

ClinPred

0.0010

GERP RS

-6.3

Varity_R

0.035

gMVP

0.32

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over