NM_001378964.1:c.330T>C

Variant names:

• chr11-126021267-A-G
• rs35131477
• NM_001378964.1:c.330T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001378964.1(CDON):​c.330T>C​(p.Pro110Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 1,614,038 control chromosomes in the GnomAD database, including 1,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (131 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1501 hom.)
• Consequence: CDON NM_001378964.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.584
• Publications: 9 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: G2P, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.016).
• BP6: Variant 11-126021267-A-G is Benign according to our data. Variant chr11-126021267-A-G is described in ClinVar as Benign. ClinVar VariationId is 95753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.584 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

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.330T>C	p.Pro110Pro	synonymous	Exon 3 of 20	NP_001365893.1
	CDON	NM_001243597.3		c.330T>C	p.Pro110Pro	synonymous	Exon 3 of 20	NP_001230526.1
	CDON	NM_001441161.1		c.330T>C	p.Pro110Pro	synonymous	Exon 3 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.330T>C	p.Pro110Pro	synonymous	Exon 3 of 20	ENSP00000432901.2
	CDON	ENST00000392693.7	TSL:1	c.330T>C	p.Pro110Pro	synonymous	Exon 3 of 20	ENSP00000376458.3
	CDON	ENST00000263577.11	TSL:1	c.330T>C	p.Pro110Pro	synonymous	Exon 3 of 20	ENSP00000263577.7

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5439 AN: 152224 Hom.: 131 Cov.: 33

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.00769

Gnomad SAS AF: 0.0482

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0436

Gnomad OTH AF: 0.0574

GnomAD2 exomes AF: 0.0373 AC: 9349 AN: 250814 AF XY: 0.0382

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.0323

Gnomad ASJ exome AF: 0.0725

Gnomad EAS exome AF: 0.00561

Gnomad FIN exome AF: 0.0136

Gnomad NFE exome AF: 0.0447

Gnomad OTH exome AF: 0.0509

GnomAD4 exome AF: 0.0426 AC: 62293 AN: 1461696 Hom.: 1501 Cov.: 33 AF XY: 0.0429 AC XY: 31191 AN XY: 727134

African (AFR) AF: 0.0218 AC: 728 AN: 33470

American (AMR) AF: 0.0334 AC: 1495 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0742 AC: 1939 AN: 26132

East Asian (EAS) AF: 0.00612 AC: 243 AN: 39688

South Asian (SAS) AF: 0.0455 AC: 3926 AN: 86240

European-Finnish (FIN) AF: 0.0150 AC: 802 AN: 53412

Middle Eastern (MID) AF: 0.0656 AC: 378 AN: 5766

European-Non Finnish (NFE) AF: 0.0450 AC: 50046 AN: 1111900

Other (OTH) AF: 0.0453 AC: 2736 AN: 60382

GnomAD4 genome AF: 0.0357 AC: 5435 AN: 152342 Hom.: 131 Cov.: 33 AF XY: 0.0348 AC XY: 2594 AN XY: 74504

African (AFR) AF: 0.0229 AC: 953 AN: 41582

American (AMR) AF: 0.0457 AC: 699 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3472

East Asian (EAS) AF: 0.00771 AC: 40 AN: 5188

South Asian (SAS) AF: 0.0485 AC: 234 AN: 4826

European-Finnish (FIN) AF: 0.0105 AC: 112 AN: 10618

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0436 AC: 2966 AN: 68032

Other (OTH) AF: 0.0568 AC: 120 AN: 2114

Alfa AF: 0.0420 Hom.: 220

Bravo AF: 0.0380

Asia WGS AF: 0.0250 AC: 89 AN: 3478

EpiCase AF: 0.0473

EpiControl AF: 0.0499

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Holoprosencephaly 11 (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.81
DANN	Benign	0.46
PhyloP100		-0.58
Mutation Taster		=99/1	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: rs35131477; hg19: chr11-125891162; COSMIC: COSV54995768; COSMIC: COSV54995768;