chr11-125978366-C-T

Position:

• chr11-125978366-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001378964.1(CDON):​c.3294G>A​(p.Thr1098Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,598,876 control chromosomes in the GnomAD database, including 109,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10640 hom., cov: 32)
  • Exomes 𝑓: 0.37 (99290 hom.)
• Consequence: CDON NM_001378964.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.325

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 11-125978366-C-T is Benign according to our data. Variant chr11-125978366-C-T is described in ClinVar as [Benign]. Clinvar id is 260793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-125978366-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.325 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDON	NM_001378964.1	c.3294G>A	p.Thr1098Thr	synonymous_variant	18/20	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6	c.3294G>A	p.Thr1098Thr	synonymous_variant	18/20	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56533 AN: 151750 Hom.: 10624 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.360

GnomAD3 exomes AF: 0.384 AC: 93281 AN: 243128 Hom.: 18008 AF XY: 0.383 AC XY: 50045 AN XY: 130792

Gnomad AFR exome AF: 0.346

Gnomad AMR exome AF: 0.445

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.384

Gnomad SAS exome AF: 0.402

Gnomad FIN exome AF: 0.420

Gnomad NFE exome AF: 0.361

Gnomad OTH exome AF: 0.383

GnomAD4 exome AF: 0.368 AC: 532225 AN: 1447008 Hom.: 99290 Cov.: 30 AF XY: 0.369 AC XY: 265159 AN XY: 719560

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.384

Gnomad4 SAS exome AF: 0.401

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.360

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.373 AC: 56589 AN: 151868 Hom.: 10640 Cov.: 32 AF XY: 0.378 AC XY: 28048 AN XY: 74202

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.361

Alfa AF: 0.365 Hom.: 14759

Bravo AF: 0.369

Asia WGS AF: 0.410 AC: 1425 AN: 3478

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
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	Jun 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	0.72
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs3740904; hg19: chr11-125848261; COSMIC: COSV54996106;