11-126001840-C-T

Position:

• chr11-126001840-C-T

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.2037G>A​(p.Ala679Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,580,472 control chromosomes in the GnomAD database, including 84,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9142 hom., cov: 32)
  • Exomes 𝑓: 0.32 (75068 hom.)
• Consequence: CDON NM_001378964.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.656

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 11-126001840-C-T is Benign according to our data. Variant chr11-126001840-C-T is described in ClinVar as [Benign]. Clinvar id is 260784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-126001840-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.656 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDON	NM_001378964.1	c.2037G>A	p.Ala679Ala	synonymous_variant	11/20	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6	c.2037G>A	p.Ala679Ala	synonymous_variant	11/20	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51818 AN: 151686 Hom.: 9124 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.316

GnomAD3 exomes AF: 0.318 AC: 79669 AN: 250898 Hom.: 12994 AF XY: 0.312 AC XY: 42364 AN XY: 135614

Gnomad AFR exome AF: 0.379

Gnomad AMR exome AF: 0.343

Gnomad ASJ exome AF: 0.376

Gnomad EAS exome AF: 0.189

Gnomad SAS exome AF: 0.264

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.325

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.319 AC: 455683 AN: 1428668 Hom.: 75068 Cov.: 29 AF XY: 0.317 AC XY: 225780 AN XY: 712312

Gnomad4 AFR exome AF: 0.379

Gnomad4 AMR exome AF: 0.343

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.316

GnomAD4 genome AF: 0.342 AC: 51881 AN: 151804 Hom.: 9142 Cov.: 32 AF XY: 0.341 AC XY: 25317 AN XY: 74156

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.321

Alfa AF: 0.334 Hom.: 5838

Bravo AF: 0.342

Asia WGS AF: 0.302 AC: 1052 AN: 3478

EpiCase AF: 0.320

EpiControl AF: 0.323

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

Holoprosencephaly 11 Benign:3

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. -
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	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.1
DANN	Benign	0.53

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: rs516664; hg19: chr11-125871735; COSMIC: COSV54996129; COSMIC: COSV54996129;