rs35131477

Positions:

• chr11-126021267-A-G

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.330T>C​(p.Pro110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,614,038 control chromosomes in the GnomAD database, including 1,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (131 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1501 hom.)
• Consequence: CDON NM_001378964.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.584

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=-0.56).
• BP6: Variant 11-126021267-A-G is Benign according to our data. Variant chr11-126021267-A-G is described in ClinVar as [Benign]. Clinvar id is 95753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-126021267-A-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.584 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1	c.330T>C	p.Pro110=	synonymous_variant	3/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6	c.330T>C	p.Pro110=	synonymous_variant	3/20	1	NM_001378964.1	P1

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5439 AN: 152224 Hom.: 131 Cov.: 33

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.00769

Gnomad SAS AF: 0.0482

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0436

Gnomad OTH AF: 0.0574

GnomAD3 exomes AF: 0.0373 AC: 9349 AN: 250814 Hom.: 251 AF XY: 0.0382 AC XY: 5183 AN XY: 135552

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.0323

Gnomad ASJ exome AF: 0.0725

Gnomad EAS exome AF: 0.00561

Gnomad SAS exome AF: 0.0450

Gnomad FIN exome AF: 0.0136

Gnomad NFE exome AF: 0.0447

Gnomad OTH exome AF: 0.0509

GnomAD4 exome AF: 0.0426 AC: 62293 AN: 1461696 Hom.: 1501 Cov.: 33 AF XY: 0.0429 AC XY: 31191 AN XY: 727134

Gnomad4 AFR exome AF: 0.0218

Gnomad4 AMR exome AF: 0.0334

Gnomad4 ASJ exome AF: 0.0742

Gnomad4 EAS exome AF: 0.00612

Gnomad4 SAS exome AF: 0.0455

Gnomad4 FIN exome AF: 0.0150

Gnomad4 NFE exome AF: 0.0450

Gnomad4 OTH exome AF: 0.0453

GnomAD4 genome AF: 0.0357 AC: 5435 AN: 152342 Hom.: 131 Cov.: 33 AF XY: 0.0348 AC XY: 2594 AN XY: 74504

Gnomad4 AFR AF: 0.0229

Gnomad4 AMR AF: 0.0457

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.00771

Gnomad4 SAS AF: 0.0485

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.0436

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0419 Hom.: 74

Bravo AF: 0.0380

Asia WGS AF: 0.0250 AC: 89 AN: 3478

EpiCase AF: 0.0473

EpiControl AF: 0.0499

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 07, 2013	- -

Holoprosencephaly 11 Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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	Invitae	Jan 29, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 07, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.81
DANN	Benign	0.46

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: rs35131477; hg19: chr11-125891162; COSMIC: COSV54995768; COSMIC: COSV54995768;