11-126001840-C-T

Variant names:

• chr11-126001840-C-T
• rs516664
• NM_001378964.1:c.2037G>A

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.2037G>A​(p.Ala679Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,580,472 control chromosomes in the GnomAD database, including 84,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9142 hom., cov: 32)
  • Exomes 𝑓: 0.32 (75068 hom.)
• Consequence: CDON NM_001378964.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.656
• Publications: 16 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=-0.53).
• BP6: Variant 11-126001840-C-T is Benign according to our data. Variant chr11-126001840-C-T is described in ClinVar as Benign. ClinVar VariationId is 260784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.656 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 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.2037G>A	p.Ala679Ala	synonymous	Exon 11 of 20	NP_001365893.1	Q4KMG0-2
	CDON	NM_001243597.3		c.2037G>A	p.Ala679Ala	synonymous	Exon 11 of 20	NP_001230526.1
	CDON	NM_001441161.1		c.2037G>A	p.Ala679Ala	synonymous	Exon 11 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.2037G>A	p.Ala679Ala	synonymous	Exon 11 of 20	ENSP00000432901.2	Q4KMG0-2
	CDON	ENST00000392693.7	TSL:1	c.2037G>A	p.Ala679Ala	synonymous	Exon 11 of 20	ENSP00000376458.3	Q4KMG0-1
	CDON	ENST00000263577.11	TSL:1	c.2037G>A	p.Ala679Ala	synonymous	Exon 11 of 20	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51818 AN: 151686 Hom.: 9124 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.316

GnomAD2 exomes AF: 0.318 AC: 79669 AN: 250898 AF XY: 0.312

Gnomad AFR exome AF: 0.379

Gnomad AMR exome AF: 0.343

Gnomad ASJ exome AF: 0.376

Gnomad EAS exome AF: 0.189

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.325

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.319 AC: 455683 AN: 1428668 Hom.: 75068 Cov.: 29 AF XY: 0.317 AC XY: 225780 AN XY: 712312

African (AFR) AF: 0.379 AC: 12534 AN: 33056

American (AMR) AF: 0.343 AC: 15301 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 9581 AN: 25880

East Asian (EAS) AF: 0.187 AC: 7407 AN: 39570

South Asian (SAS) AF: 0.263 AC: 22551 AN: 85696

European-Finnish (FIN) AF: 0.350 AC: 18651 AN: 53304

Middle Eastern (MID) AF: 0.273 AC: 1567 AN: 5732

European-Non Finnish (NFE) AF: 0.323 AC: 349366 AN: 1081448

Other (OTH) AF: 0.316 AC: 18725 AN: 59316

GnomAD4 genome AF: 0.342 AC: 51881 AN: 151804 Hom.: 9142 Cov.: 32 AF XY: 0.341 AC XY: 25317 AN XY: 74156

African (AFR) AF: 0.380 AC: 15699 AN: 41336

American (AMR) AF: 0.362 AC: 5531 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1276 AN: 3464

East Asian (EAS) AF: 0.180 AC: 930 AN: 5156

South Asian (SAS) AF: 0.263 AC: 1266 AN: 4806

European-Finnish (FIN) AF: 0.345 AC: 3622 AN: 10496

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.329 AC: 22372 AN: 67958

Other (OTH) AF: 0.321 AC: 677 AN: 2108

Alfa AF: 0.333 Hom.: 7642

Bravo AF: 0.342

Asia WGS AF: 0.302 AC: 1052 AN: 3478

EpiCase AF: 0.320

EpiControl AF: 0.323

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	-0.53
CADD	Benign	8.1
DANN	Benign	0.53
PhyloP100		-0.66
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: rs516664; hg19: chr11-125871735; COSMIC: COSV54996129; COSMIC: COSV54996129;