11-125981160-A-C

Variant names:

• chr11-125981160-A-C
• rs564214
• NM_001378964.1:c.3165T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001378964.1(CDON):​c.3165T>G​(p.Asn1055Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1055S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CDON NM_001378964.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 20 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: Illumina, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	NM_001378964.1	MANE Select	c.3165T>G	p.Asn1055Lys	missense	Exon 17 of 20	NP_001365893.1	Q4KMG0-2
	CDON	NM_001243597.3		c.3165T>G	p.Asn1055Lys	missense	Exon 17 of 20	NP_001230526.1
	CDON	NM_001441161.1		c.3165T>G	p.Asn1055Lys	missense	Exon 17 of 20	NP_001428090.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	ENST00000531738.6	TSL:1 MANE Select	c.3165T>G	p.Asn1055Lys	missense	Exon 17 of 20	ENSP00000432901.2	Q4KMG0-2
	CDON	ENST00000392693.7	TSL:1	c.3165T>G	p.Asn1055Lys	missense	Exon 17 of 20	ENSP00000376458.3	Q4KMG0-1
	CDON	ENST00000263577.11	TSL:1	c.3165T>G	p.Asn1055Lys	missense	Exon 17 of 20	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461874 Hom.: 0 Cov.: 37 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.061
DANN	Benign	0.96
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.085	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-1.9
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.019	D
Polyphen		0.99	D
Vest4		0.49
MutPred		0.32		Gain of methylation at N1055 (P = 0.0203)
MVP		0.77
MPC		0.34
ClinPred		0.71	D
GERP RS		-4.4
Varity_R		0.090
gMVP		0.67
Mutation Taster		=89/11	polymorphism

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: rs564214; hg19: chr11-125851055; COSMIC: COSV54995918;