rs2276061

Variant names:

• chr11-125961806-G-A
• rs2276061
• NM_001378964.1:c.3549C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-125961806-G-A
• chr11-125961806-G-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.3549C>T​(p.Val1183Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,642 control chromosomes in the GnomAD database, including 75,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5470 hom., cov: 33)
  • Exomes 𝑓: 0.31 (70210 hom.)
• Consequence: CDON NM_001378964.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0530
• Publications: 24 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-125961806-G-A is Benign according to our data. Variant chr11-125961806-G-A is described in ClinVar as Benign. ClinVar VariationId is 260797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.053 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 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.3549C>T	p.Val1183Val	synonymous	Exon 19 of 20	NP_001365893.1	Q4KMG0-2
	CDON	NM_001243597.3		c.3549C>T	p.Val1183Val	synonymous	Exon 19 of 20	NP_001230526.1
	CDON	NM_001441161.1		c.3549C>T	p.Val1183Val	synonymous	Exon 19 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.3549C>T	p.Val1183Val	synonymous	Exon 19 of 20	ENSP00000432901.2	Q4KMG0-2
	CDON	ENST00000392693.7	TSL:1	c.3549C>T	p.Val1183Val	synonymous	Exon 19 of 20	ENSP00000376458.3	Q4KMG0-1
	CDON	ENST00000263577.11	TSL:1	c.3549C>T	p.Val1183Val	synonymous	Exon 19 of 20	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38709 AN: 151982 Hom.: 5468 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.251

GnomAD2 exomes AF: 0.290 AC: 72946 AN: 251112 AF XY: 0.296

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.276

Gnomad ASJ exome AF: 0.287

Gnomad EAS exome AF: 0.274

Gnomad FIN exome AF: 0.317

Gnomad NFE exome AF: 0.309

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.307 AC: 449354 AN: 1461542 Hom.: 70210 Cov.: 37 AF XY: 0.308 AC XY: 224079 AN XY: 727070

African (AFR) AF: 0.116 AC: 3891 AN: 33478

American (AMR) AF: 0.274 AC: 12264 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 7710 AN: 26136

East Asian (EAS) AF: 0.279 AC: 11091 AN: 39694

South Asian (SAS) AF: 0.318 AC: 27440 AN: 86248

European-Finnish (FIN) AF: 0.311 AC: 16627 AN: 53404

Middle Eastern (MID) AF: 0.251 AC: 1445 AN: 5768

European-Non Finnish (NFE) AF: 0.316 AC: 350788 AN: 1111728

Other (OTH) AF: 0.300 AC: 18098 AN: 60388

GnomAD4 genome AF: 0.255 AC: 38729 AN: 152100 Hom.: 5470 Cov.: 33 AF XY: 0.257 AC XY: 19090 AN XY: 74340

African (AFR) AF: 0.126 AC: 5228 AN: 41504

American (AMR) AF: 0.264 AC: 4035 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1021 AN: 3472

East Asian (EAS) AF: 0.283 AC: 1459 AN: 5156

South Asian (SAS) AF: 0.314 AC: 1511 AN: 4808

European-Finnish (FIN) AF: 0.319 AC: 3371 AN: 10554

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21224 AN: 68002

Other (OTH) AF: 0.250 AC: 529 AN: 2112

Alfa AF: 0.291 Hom.: 10507

Bravo AF: 0.246

Asia WGS AF: 0.271 AC: 944 AN: 3478

EpiCase AF: 0.311

EpiControl AF: 0.314

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Holoprosencephaly 11 (3)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.34
DANN	Benign	0.71
PhyloP100		-0.053
Mutation Taster		=100/0	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: rs2276061; hg19: chr11-125831701; COSMIC: COSV54997153; COSMIC: COSV54997153;