11-126021208-C-CA

Variant names:

• chr11-126021208-C-CA
• rs3832751
• NM_001378964.1:c.349+39dupT

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.349+39dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,606,576 control chromosomes in the GnomAD database, including 46,423 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7384 hom., cov: 14)
  • Exomes 𝑓: 0.23 (39039 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.399
• Publications: 3 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 11-126021208-C-CA is Benign according to our data. Variant chr11-126021208-C-CA is described in ClinVar as Benign. ClinVar VariationId is 260794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.349+39dupT		intron_variant	Intron 3 of 19	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6	c.349+39_349+40insT		intron_variant	Intron 3 of 19	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44594 AN: 151766 Hom.: 7370 Cov.: 14

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.228

GnomAD2 exomes AF: 0.239 AC: 58089 AN: 242808 AF XY: 0.234

Gnomad AFR exome AF: 0.452

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.142

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.219

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.226 AC: 328781 AN: 1454692 Hom.: 39039 Cov.: 30 AF XY: 0.224 AC XY: 162339 AN XY: 723894

African (AFR) AF: 0.457 AC: 15223 AN: 33290

American (AMR) AF: 0.229 AC: 10195 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 6542 AN: 26052

East Asian (EAS) AF: 0.146 AC: 5769 AN: 39600

South Asian (SAS) AF: 0.195 AC: 16698 AN: 85530

European-Finnish (FIN) AF: 0.345 AC: 18080 AN: 52394

Middle Eastern (MID) AF: 0.192 AC: 1104 AN: 5748

European-Non Finnish (NFE) AF: 0.218 AC: 241477 AN: 1107424

Other (OTH) AF: 0.228 AC: 13693 AN: 60148

GnomAD4 genome AF: 0.294 AC: 44639 AN: 151884 Hom.: 7384 Cov.: 14 AF XY: 0.298 AC XY: 22101 AN XY: 74226

African (AFR) AF: 0.452 AC: 18709 AN: 41364

American (AMR) AF: 0.233 AC: 3565 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 844 AN: 3464

East Asian (EAS) AF: 0.159 AC: 823 AN: 5174

South Asian (SAS) AF: 0.200 AC: 960 AN: 4810

European-Finnish (FIN) AF: 0.371 AC: 3908 AN: 10526

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14983 AN: 67960

Other (OTH) AF: 0.226 AC: 476 AN: 2106

Alfa AF: 0.256 Hom.: 1109

Bravo AF: 0.289

Asia WGS AF: 0.201 AC: 701 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.40
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: rs3832751; hg19: chr11-125891103; COSMIC: COSV54997835; COSMIC: COSV54997835;