11-125995077-AAACAAC-AAAC

Variant names:

• chr11-125995077-AAAC-A
• rs138741332
• NM_001378964.1:c.2363-28_2363-26delGTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001378964.1(CDON):​c.2363-28_2363-26delGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,565,838 control chromosomes in the GnomAD database, including 58,667 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4827 hom., cov: 25)
  • Exomes 𝑓: 0.27 (53840 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.44
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 11-125995077-AAAC-A is Benign according to our data. Variant chr11-125995077-AAAC-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 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.2363-28_2363-26delGTT		intron	N/A	NP_001365893.1	Q4KMG0-2
	CDON	NM_001243597.3		c.2363-28_2363-26delGTT		intron	N/A	NP_001230526.1
	CDON	NM_001441161.1		c.2363-28_2363-26delGTT		intron	N/A	NP_001428090.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	ENST00000531738.6	TSL:1 MANE Select	c.2363-28_2363-26delGTT		intron	N/A	ENSP00000432901.2	Q4KMG0-2
	CDON	ENST00000392693.7	TSL:1	c.2363-28_2363-26delGTT		intron	N/A	ENSP00000376458.3	Q4KMG0-1
	CDON	ENST00000263577.11	TSL:1	c.2363-28_2363-26delGTT		intron	N/A	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36890 AN: 151892 Hom.: 4827 Cov.: 25

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.281

GnomAD2 exomes AF: 0.277 AC: 68414 AN: 246792 AF XY: 0.279

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.307

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.479

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.269

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.267 AC: 377174 AN: 1413828 Hom.: 53840 AF XY: 0.268 AC XY: 189309 AN XY: 706356

African (AFR) AF: 0.143 AC: 4673 AN: 32596

American (AMR) AF: 0.305 AC: 13565 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 5831 AN: 25890

East Asian (EAS) AF: 0.501 AC: 19735 AN: 39364

South Asian (SAS) AF: 0.267 AC: 22708 AN: 85156

European-Finnish (FIN) AF: 0.239 AC: 12535 AN: 52476

Middle Eastern (MID) AF: 0.280 AC: 1432 AN: 5108

European-Non Finnish (NFE) AF: 0.263 AC: 281250 AN: 1069918

Other (OTH) AF: 0.263 AC: 15445 AN: 58780

GnomAD4 genome AF: 0.243 AC: 36897 AN: 152010 Hom.: 4827 Cov.: 25 AF XY: 0.244 AC XY: 18134 AN XY: 74294

African (AFR) AF: 0.151 AC: 6269 AN: 41498

American (AMR) AF: 0.277 AC: 4220 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 792 AN: 3470

East Asian (EAS) AF: 0.478 AC: 2459 AN: 5140

South Asian (SAS) AF: 0.283 AC: 1363 AN: 4822

European-Finnish (FIN) AF: 0.245 AC: 2584 AN: 10564

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18347 AN: 67954

Other (OTH) AF: 0.278 AC: 585 AN: 2106

Alfa AF: 0.180 Hom.: 534

Bravo AF: 0.246

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4
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: rs138741332; hg19: chr11-125864972;