rs35884952

chr11-126005939-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001378964.1(CDON):c.1671G>A(p.Lys557=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,614,058 control chromosomes in the GnomAD database, including 468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (33 hom., cov: 32)
  • Exomes 𝑓: 0.023 (435 hom.)
• Consequence: CDON NM_001378964.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0280

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=-0.71).
• BP6: Variant 11-126005939-C-T is Benign according to our data. Variant chr11-126005939-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-126005939-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.028 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.017 (2586/152212) while in subpopulation NFE AF= 0.0263 (1785/67996). AF 95% confidence interval is 0.0252. There are 33 homozygotes in gnomad4. There are 1235 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2586 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1	c.1671G>A	p.Lys557=	synonymous_variant	9/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6	c.1671G>A	p.Lys557=	synonymous_variant	9/20	1	NM_001378964.1	P1

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2586 AN: 152094 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00406

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.0181 AC: 4544 AN: 251110 Hom.: 61 AF XY: 0.0182 AC XY: 2464 AN XY: 135710

Gnomad AFR exome AF: 0.00400

Gnomad AMR exome AF: 0.00954

Gnomad ASJ exome AF: 0.0156

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00630

Gnomad FIN exome AF: 0.0315

Gnomad NFE exome AF: 0.0266

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0229 AC: 33517 AN: 1461846 Hom.: 435 Cov.: 32 AF XY: 0.0223 AC XY: 16231 AN XY: 727230

Gnomad4 AFR exome AF: 0.00338

Gnomad4 AMR exome AF: 0.00937

Gnomad4 ASJ exome AF: 0.0168

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00636

Gnomad4 FIN exome AF: 0.0322

Gnomad4 NFE exome AF: 0.0261

Gnomad4 OTH exome AF: 0.0199

GnomAD4 genome AF: 0.0170 AC: 2586 AN: 152212 Hom.: 33 Cov.: 32 AF XY: 0.0166 AC XY: 1235 AN XY: 74448

Gnomad4 AFR AF: 0.00404

Gnomad4 AMR AF: 0.00994

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.0326

Gnomad4 NFE AF: 0.0263

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0235 Hom.: 17

Bravo AF: 0.0151

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0234

EpiControl AF: 0.0247

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Holoprosencephaly 11 Benign:2

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	Invitae	Jan 29, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	3.1
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: rs35884952; hg19: chr11-125875834; COSMIC: COSV54994958; COSMIC: COSV54994958;