rs387906995

Positions:

• chr11-126001812-G-A
• chr11-126001812-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PM5 BP4

The NM_001378964.1(CDON):​c.2065C>T​(p.Pro689Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P689A) has been classified as Likely pathogenic.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 32)
• Consequence: CDON NM_001378964.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.20

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr11-126001812-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 30747.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.40950295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1	c.2065C>T	p.Pro689Ser	missense_variant	11/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6	c.2065C>T	p.Pro689Ser	missense_variant	11/20	1	NM_001378964.1	P1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.3	M;.;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.4	N;D;N
REVEL	Benign	0.16
Sift	Uncertain	0.012	D;D;D
Sift4G	Benign	0.069	T;D;T
Polyphen		0.99	D;P;D
Vest4		0.52
MutPred		0.26		Loss of catalytic residue at P689 (P = 0.0182);.;Loss of catalytic residue at P689 (P = 0.0182);
MVP		0.82
MPC		0.23
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.097
gMVP		0.46

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: rs387906995; hg19: chr11-125871707;