rs3737336

Variant names:

• chr11-125960802-T-C
• rs3737336
• NM_001378964.1:c.*140A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001378964.1(CDON):​c.*140A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.293 in 790,096 control chromosomes in the GnomAD database, including 35,027 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5477 hom., cov: 32)
  • Exomes 𝑓: 0.30 (29550 hom.)
• Consequence: CDON NM_001378964.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.78
• Publications: 23 publications found

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 Gene-Disease associations (from GenCC):

• holoprosencephaly 11

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 11-125960802-T-C is Benign according to our data. Variant chr11-125960802-T-C is described in ClinVar as Benign. ClinVar VariationId is 303488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378964.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	NM_001378964.1	MANE Select	c.*140A>G		3_prime_UTR	Exon 20 of 20	NP_001365893.1
	CDON	NM_001243597.3		c.*140A>G		3_prime_UTR	Exon 20 of 20	NP_001230526.1
	CDON	NM_001441161.1		c.*140A>G		3_prime_UTR	Exon 20 of 20	NP_001428090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	ENST00000531738.6	TSL:1 MANE Select	c.*140A>G		3_prime_UTR	Exon 20 of 20	ENSP00000432901.2
	CDON	ENST00000392693.7	TSL:1	c.*140A>G		3_prime_UTR	Exon 20 of 20	ENSP00000376458.3
	CDON	ENST00000263577.11	TSL:1	c.*140A>G		3_prime_UTR	Exon 20 of 20	ENSP00000263577.7

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38761 AN: 152022 Hom.: 5475 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.302 AC: 192349 AN: 637956 Hom.: 29550 Cov.: 8 AF XY: 0.304 AC XY: 103436 AN XY: 340620

African (AFR) AF: 0.122 AC: 2090 AN: 17094

American (AMR) AF: 0.278 AC: 10170 AN: 36590

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 5460 AN: 18388

East Asian (EAS) AF: 0.279 AC: 9894 AN: 35498

South Asian (SAS) AF: 0.316 AC: 19331 AN: 61178

European-Finnish (FIN) AF: 0.311 AC: 15581 AN: 50064

Middle Eastern (MID) AF: 0.256 AC: 614 AN: 2396

European-Non Finnish (NFE) AF: 0.312 AC: 119654 AN: 384004

Other (OTH) AF: 0.292 AC: 9555 AN: 32744

GnomAD4 genome AF: 0.255 AC: 38780 AN: 152140 Hom.: 5477 Cov.: 32 AF XY: 0.257 AC XY: 19095 AN XY: 74356

African (AFR) AF: 0.126 AC: 5246 AN: 41526

American (AMR) AF: 0.264 AC: 4037 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1467 AN: 5170

South Asian (SAS) AF: 0.314 AC: 1512 AN: 4822

European-Finnish (FIN) AF: 0.318 AC: 3363 AN: 10562

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21254 AN: 67980

Other (OTH) AF: 0.250 AC: 530 AN: 2116

Alfa AF: 0.299 Hom.: 19859

Bravo AF: 0.247

Asia WGS AF: 0.271 AC: 944 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Apr 12, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Holoprosencephaly 11 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	16
DANN	Benign	0.87
PhyloP100		4.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3737336; hg19: chr11-125830697; COSMIC: COSV54997022; COSMIC: COSV54997022;