rs12274923

Positions:

chr11-126001820-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378964.1(CDON):c.2057C>T(p.Ala686Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,595,034 control chromosomes in the GnomAD database, including 26,783 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2116 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24667 hom. )

Consequence

CDON
NM_001378964.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.53

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001748234).

BP6

Variant 11-126001820-G-A is Benign according to our data. Variant chr11-126001820-G-A is described in ClinVar as [Benign]. Clinvar id is 260785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDON	NM_001378964.1 linkuse as main transcript	c.2057C>T	p.Ala686Val	missense_variant	11/20	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6 linkuse as main transcript	c.2057C>T	p.Ala686Val	missense_variant	11/20	1	NM_001378964.1	ENSP00000432901	P1	Q4KMG0-2

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24260

AN:

152022

Hom.:

2111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0935

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.0708

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.167

AC:

41836

AN:

251156

Hom.:

3700

AF XY:

0.167

AC XY:

22705

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.0890

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.0710

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.180

AC:

259760

AN:

1442894

Hom.:

24667

Cov.:

AF XY:

0.179

AC XY:

128853

AN XY:

718742

show subpopulations

Gnomad4 AFR exome

AF:

0.0838

Gnomad4 AMR exome

AF:

0.158

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.0739

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.189

Gnomad4 OTH exome

AF:

0.169

GnomAD4 genome

AF:

0.160

AC:

24289

AN:

152140

Hom.:

2116

Cov.:

AF XY:

0.159

AC XY:

11855

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0935

Gnomad4 AMR

AF:

0.163

Gnomad4 ASJ

AF:

0.216

Gnomad4 EAS

AF:

0.0704

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.213

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.178

Hom.:

2750

Bravo

AF:

0.150

TwinsUK

AF:

0.198

AC:

733

ALSPAC

AF:

0.190

AC:

732

ESP6500AA

AF:

0.102

AC:

451

ESP6500EA

AF:

0.192

AC:

1653

ExAC

AF:

0.163

AC:

19809

Asia WGS

AF:

0.133

AC:

464

AN:

3478

EpiCase

AF:

0.181

EpiControl

AF:

0.183

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Holoprosencephaly 11

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.79

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;M

MutationTaster

Benign

0.13

P;P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.22

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.082

T;D;T

Sift4G

Benign

0.084

T;T;T

Polyphen

0.95

P;P;D

Vest4

0.096

MPC

0.10

ClinPred

0.017

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.032

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over