rs564214

Positions:

• chr11-125981160-A-C
• chr11-125981160-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1	c.3165T>G	p.Asn1055Lys	missense_variant	17/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6	c.3165T>G	p.Asn1055Lys	missense_variant	17/20	1	NM_001378964.1	P1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Uncertain	0.085	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.6	M;.;M
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.019	D;D;D
Polyphen		0.99	D;P;D
Vest4		0.49
MutPred		0.32		Gain of methylation at N1055 (P = 0.0203);.;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

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

Publications

LitVar

Other links and lift over

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