NM_001378964.1:c.350-13T>C

Variant names:

• chr11-126019778-A-G
• rs3740910
• NM_001378964.1:c.350-13T>C

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.350-13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 1,601,770 control chromosomes in the GnomAD database, including 7,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (863 hom., cov: 32)
  • Exomes 𝑓: 0.091 (6385 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.647
• Publications: 6 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=-0.83).
• BP6: Variant 11-126019778-A-G is Benign according to our data. Variant chr11-126019778-A-G is described in ClinVar as Benign. ClinVar VariationId is 260795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.350-13T>C		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.350-13T>C		intron_variant	Intron 3 of 19	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15804 AN: 152130 Hom.: 860 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.109 AC: 27022 AN: 248602 AF XY: 0.107

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.136

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.0859

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.0913 AC: 132284 AN: 1449522 Hom.: 6385 Cov.: 28 AF XY: 0.0916 AC XY: 66124 AN XY: 721940

African (AFR) AF: 0.111 AC: 3687 AN: 33198

American (AMR) AF: 0.141 AC: 6294 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2675 AN: 26068

East Asian (EAS) AF: 0.123 AC: 4856 AN: 39608

South Asian (SAS) AF: 0.116 AC: 9964 AN: 86024

European-Finnish (FIN) AF: 0.125 AC: 6604 AN: 52698

Middle Eastern (MID) AF: 0.0709 AC: 396 AN: 5588

European-Non Finnish (NFE) AF: 0.0835 AC: 91984 AN: 1101694

Other (OTH) AF: 0.0971 AC: 5824 AN: 59972

GnomAD4 genome AF: 0.104 AC: 15836 AN: 152248 Hom.: 863 Cov.: 32 AF XY: 0.106 AC XY: 7888 AN XY: 74450

African (AFR) AF: 0.114 AC: 4737 AN: 41534

American (AMR) AF: 0.126 AC: 1930 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3470

East Asian (EAS) AF: 0.122 AC: 634 AN: 5182

South Asian (SAS) AF: 0.122 AC: 588 AN: 4822

European-Finnish (FIN) AF: 0.127 AC: 1347 AN: 10608

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0879 AC: 5978 AN: 68018

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.0954 Hom.: 143

Bravo AF: 0.103

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

Holoprosencephaly 11 Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 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. -

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	-0.83
CADD	Benign	5.3
DANN	Benign	0.72
PhyloP100		-0.65
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: rs3740910; hg19: chr11-125889673; COSMIC: COSV54996157; COSMIC: COSV54996157;