11-126021374-C-T

Position:

chr11-126021374-C-T

Variant summary

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

The NM_001378964.1(CDON):c.223G>A(p.Val75Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,613,614 control chromosomes in the GnomAD database, including 262,028 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31463 hom., cov: 31)

Exomes 𝑓: 0.56 ( 230565 hom. )

Consequence

CDON
NM_001378964.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.22

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:

CDON (HGNC:):

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=9.736624E-7).

BP6

Variant 11-126021374-C-T is Benign according to our data. Variant chr11-126021374-C-T is described in ClinVar as [Benign]. Clinvar id is 95752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-126021374-C-T is described in Lovd as [Benign]. Variant chr11-126021374-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 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.223G>A	p.Val75Ile	missense_variant	3/20	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.223G>A	p.Val75Ile	missense_variant	3/20	1	NM_001378964.1	ENSP00000432901.2		Q4KMG0-2E9PN78

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95653

AN:

151916

Hom.:

31412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.814

Gnomad AMI

AF:

0.708

Gnomad AMR

AF:

0.561

Gnomad ASJ

AF:

0.591

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.645

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.572

GnomAD3 exomes

AF:

0.554

AC:

139325

AN:

251292

Hom.:

40038

AF XY:

0.551

AC XY:

74768

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.820

Gnomad AMR exome

AF:

0.504

Gnomad ASJ exome

AF:

0.612

Gnomad EAS exome

AF:

0.319

Gnomad SAS exome

AF:

0.528

Gnomad FIN exome

AF:

0.635

Gnomad NFE exome

AF:

0.556

Gnomad OTH exome

AF:

0.555

GnomAD4 exome

AF:

0.558

AC:

814980

AN:

1461580

Hom.:

230565

Cov.:

AF XY:

0.556

AC XY:

404346

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.825

Gnomad4 AMR exome

AF:

0.508

Gnomad4 ASJ exome

AF:

0.605

Gnomad4 EAS exome

AF:

0.303

Gnomad4 SAS exome

AF:

0.528

Gnomad4 FIN exome

AF:

0.628

Gnomad4 NFE exome

AF:

0.558

Gnomad4 OTH exome

AF:

0.569

GnomAD4 genome

AF:

0.630

AC:

95762

AN:

152034

Hom.:

31463

Cov.:

AF XY:

0.628

AC XY:

46668

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.815

Gnomad4 AMR

AF:

0.560

Gnomad4 ASJ

AF:

0.591

Gnomad4 EAS

AF:

0.319

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.645

Gnomad4 NFE

AF:

0.564

Gnomad4 OTH

AF:

0.571

Alfa

AF:

0.567

Hom.:

64696

Bravo

AF:

0.628

TwinsUK

AF:

0.552

AC:

2045

ALSPAC

AF:

0.547

AC:

2109

ESP6500AA

AF:

0.802

AC:

3530

ESP6500EA

AF:

0.565

AC:

4857

ExAC

AF:

0.557

AC:

67644

Asia WGS

AF:

0.489

AC:

1699

AN:

3478

EpiCase

AF:

0.559

EpiControl

AF:

0.558

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 03, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Holoprosencephaly 11

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 09, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.7

DANN

Benign

0.20

DEOGEN2

Benign

0.21

T;.;.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.21

T;T;T;T;T

MetaRNN

Benign

9.7e-7

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.65

N;N;.;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.28

N;N;N;N;N

REVEL

Benign

0.058

Sift

Benign

0.79

T;T;T;T;T

Sift4G

Benign

0.62

T;T;.;.;.

Polyphen

0.0010

B;B;B;.;.

Vest4

0.024

MPC

0.081

ClinPred

0.0019

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.046

gMVP

0.22

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

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