11-125984047-A-T

Variant names:

• chr11-125984047-A-T
• NM_001378964.1:c.2820T>A
• CDON p.Ser940Arg

Variant summary

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

The NM_001378964.1(CDON):​c.2820T>A​(p.Ser940Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDON NM_001378964.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816
• Publications: 0 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: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae), G2P
• 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.2820T>A	p.Ser940Arg	missense	Exon 16 of 20	NP_001365893.1	Q4KMG0-2
	CDON	NM_001243597.3		c.2820T>A	p.Ser940Arg	missense	Exon 16 of 20	NP_001230526.1
	CDON	NM_001441161.1		c.2820T>A	p.Ser940Arg	missense	Exon 16 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.2820T>A	p.Ser940Arg	missense	Exon 16 of 20	ENSP00000432901.2	Q4KMG0-2
	CDON	ENST00000392693.7	TSL:1	c.2820T>A	p.Ser940Arg	missense	Exon 16 of 20	ENSP00000376458.3	Q4KMG0-1
	CDON	ENST00000263577.11	TSL:1	c.2820T>A	p.Ser940Arg	missense	Exon 16 of 20	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	0.0089	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.82
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.38
Sift	Benign	0.049	D
Sift4G	Benign	0.18	T
Varity_R		0.32
gMVP		0.55
Mutation Taster		=65/35	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-125853942;