rs2276061

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378964.1(CDON):​c.3549C>T​(p.Val1183=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,642 control chromosomes in the GnomAD database, including 75,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5470 hom., cov: 33)
Exomes 𝑓: 0.31 ( 70210 hom. )

Consequence

CDON
NM_001378964.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0530
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 11-125961806-G-A is Benign according to our data. Variant chr11-125961806-G-A is described in ClinVar as [Benign]. Clinvar id is 260797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-125961806-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.053 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDONNM_001378964.1 linkuse as main transcriptc.3549C>T p.Val1183= synonymous_variant 19/20 ENST00000531738.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDONENST00000531738.6 linkuse as main transcriptc.3549C>T p.Val1183= synonymous_variant 19/201 NM_001378964.1 P1Q4KMG0-2

Frequencies

GnomAD3 genomes
AF:
0.255
AC:
38709
AN:
151982
Hom.:
5468
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.126
Gnomad AMI
AF:
0.302
Gnomad AMR
AF:
0.264
Gnomad ASJ
AF:
0.294
Gnomad EAS
AF:
0.283
Gnomad SAS
AF:
0.314
Gnomad FIN
AF:
0.319
Gnomad MID
AF:
0.250
Gnomad NFE
AF:
0.312
Gnomad OTH
AF:
0.251
GnomAD3 exomes
AF:
0.290
AC:
72946
AN:
251112
Hom.:
10938
AF XY:
0.296
AC XY:
40213
AN XY:
135730
show subpopulations
Gnomad AFR exome
AF:
0.122
Gnomad AMR exome
AF:
0.276
Gnomad ASJ exome
AF:
0.287
Gnomad EAS exome
AF:
0.274
Gnomad SAS exome
AF:
0.316
Gnomad FIN exome
AF:
0.317
Gnomad NFE exome
AF:
0.309
Gnomad OTH exome
AF:
0.306
GnomAD4 exome
AF:
0.307
AC:
449354
AN:
1461542
Hom.:
70210
Cov.:
37
AF XY:
0.308
AC XY:
224079
AN XY:
727070
show subpopulations
Gnomad4 AFR exome
AF:
0.116
Gnomad4 AMR exome
AF:
0.274
Gnomad4 ASJ exome
AF:
0.295
Gnomad4 EAS exome
AF:
0.279
Gnomad4 SAS exome
AF:
0.318
Gnomad4 FIN exome
AF:
0.311
Gnomad4 NFE exome
AF:
0.316
Gnomad4 OTH exome
AF:
0.300
GnomAD4 genome
AF:
0.255
AC:
38729
AN:
152100
Hom.:
5470
Cov.:
33
AF XY:
0.257
AC XY:
19090
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.126
Gnomad4 AMR
AF:
0.264
Gnomad4 ASJ
AF:
0.294
Gnomad4 EAS
AF:
0.283
Gnomad4 SAS
AF:
0.314
Gnomad4 FIN
AF:
0.319
Gnomad4 NFE
AF:
0.312
Gnomad4 OTH
AF:
0.250
Alfa
AF:
0.298
Hom.:
8780
Bravo
AF:
0.246
Asia WGS
AF:
0.271
AC:
944
AN:
3478
EpiCase
AF:
0.311
EpiControl
AF:
0.314

ClinVar

Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Holoprosencephaly 11 Benign:3
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 22, 2021- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxDec 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.34
DANN
Benign
0.71

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.

Other links and lift over

dbSNP: rs2276061; hg19: chr11-125831701; COSMIC: COSV54997153; COSMIC: COSV54997153; API