chr11-126021400-T-C

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.197A>G(p.Lys66Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 1,614,090 control chromosomes in the GnomAD database, including 269 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 0.024 ( 146 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 123 hom. )

Consequence

CDON
NM_001378964.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.26

Publications

8 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=0.002622813).

BP6

Variant 11-126021400-T-C is Benign according to our data. Variant chr11-126021400-T-C is described in ClinVar as Benign. ClinVar VariationId is 303523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0795 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.197A>G	p.Lys66Arg	missense	Exon 3 of 20	NP_001365893.1	Q4KMG0-2
CDON	NM_001243597.3		c.197A>G	p.Lys66Arg	missense	Exon 3 of 20	NP_001230526.1
CDON	NM_001441161.1		c.197A>G	p.Lys66Arg	missense	Exon 3 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.197A>G	p.Lys66Arg	missense	Exon 3 of 20	ENSP00000432901.2	Q4KMG0-2
CDON	ENST00000392693.7	TSL:1	c.197A>G	p.Lys66Arg	missense	Exon 3 of 20	ENSP00000376458.3	Q4KMG0-1
CDON	ENST00000263577.11	TSL:1	c.197A>G	p.Lys66Arg	missense	Exon 3 of 20	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes

AF:

0.0235

AC:

3574

AN:

152130

Hom.:

144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0816

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00825

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00663

AC:

1666

AN:

251364

AF XY:

0.00484

show subpopulations

Gnomad AFR exome

AF:

0.0883

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000369

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00250

AC:

3661

AN:

1461842

Hom.:

123

Cov.:

AF XY:

0.00216

AC XY:

1568

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0833

AC:

2787

AN:

33462

American (AMR)

AF:

0.00519

AC:

232

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000185

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000281

AC:

312

AN:

1111988

Other (OTH)

AF:

0.00493

AC:

298

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

182

363

545

726

908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.0236

AC:

3591

AN:

152248

Hom.:

146

Cov.:

AF XY:

0.0228

AC XY:

1698

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0818

AC:

3397

AN:

41526

American (AMR)

AF:

0.00817

AC:

125

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68020

Other (OTH)

AF:

0.0151

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

165

329

494

658

823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.00947

Hom.:

150

Bravo

AF:

0.0273

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0888

AC:

391

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.00795

AC:

965

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000415

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

0.10

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.23

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.66

PhyloP100

3.3

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.86

REVEL

Benign

0.076

Sift

Benign

0.072

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.055

MVP

0.25

MPC

0.079

ClinPred

0.0046

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.062

gMVP

0.32

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over