chr11-125961806-G-A

Position:

• chr11-125961806-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0530

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]

ACMG classification

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
CDON	NM_001378964.1	c.3549C>T	p.Val1183=	synonymous_variant	19/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6	c.3549C>T	p.Val1183=	synonymous_variant	19/20	1	NM_001378964.1	P1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38709 AN: 151982 Hom.: 5468 Cov.: 33

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

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

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

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

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Holoprosencephaly 11 Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 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. -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 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

Other links and lift over

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