11-126023380-C-T

Variant names:

• chr11-126023380-C-T
• rs1939890
• NM_001378964.1:c.76+21G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378964.1(CDON):​c.76+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,515,102 control chromosomes in the GnomAD database, including 26,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2384 hom., cov: 32)
  • Exomes 𝑓: 0.19 (24548 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.27
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-126023380-C-T is Benign according to our data. Variant chr11-126023380-C-T is described in ClinVar as Benign. ClinVar VariationId is 260805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.76+21G>A		intron_variant	Intron 2 of 19	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6	c.76+21G>A		intron_variant	Intron 2 of 19	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25891 AN: 151860 Hom.: 2384 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.183 AC: 46041 AN: 251086 AF XY: 0.184

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.179

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.174

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.187 AC: 255288 AN: 1363124 Hom.: 24548 Cov.: 22 AF XY: 0.188 AC XY: 128550 AN XY: 684154

African (AFR) AF: 0.111 AC: 3495 AN: 31462

American (AMR) AF: 0.177 AC: 7903 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 5015 AN: 25540

East Asian (EAS) AF: 0.158 AC: 6219 AN: 39248

South Asian (SAS) AF: 0.203 AC: 17103 AN: 84388

European-Finnish (FIN) AF: 0.199 AC: 10642 AN: 53348

Middle Eastern (MID) AF: 0.125 AC: 696 AN: 5554

European-Non Finnish (NFE) AF: 0.189 AC: 193432 AN: 1021874

Other (OTH) AF: 0.189 AC: 10783 AN: 57080

GnomAD4 genome AF: 0.171 AC: 25918 AN: 151978 Hom.: 2384 Cov.: 32 AF XY: 0.171 AC XY: 12690 AN XY: 74256

African (AFR) AF: 0.116 AC: 4824 AN: 41474

American (AMR) AF: 0.178 AC: 2716 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3472

East Asian (EAS) AF: 0.159 AC: 821 AN: 5148

South Asian (SAS) AF: 0.206 AC: 988 AN: 4798

European-Finnish (FIN) AF: 0.199 AC: 2102 AN: 10550

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.195 AC: 13233 AN: 67978

Other (OTH) AF: 0.160 AC: 338 AN: 2114

Alfa AF: 0.178 Hom.: 4760

Bravo AF: 0.163

Asia WGS AF: 0.229 AC: 796 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

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.63
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1939890; hg19: chr11-125893275; COSMIC: COSV54998277; COSMIC: COSV54998277;