11-125997158-G-T

Variant names:

• chr11-125997158-G-T
• rs11220309
• NM_001378964.1:c.2362+49C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378964.1(CDON):​c.2362+49C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 1,297,830 control chromosomes in the GnomAD database, including 556,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (65617 hom., cov: 32)
  • Exomes 𝑓: 0.93 (490873 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.78
• Publications: 5 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 11-125997158-G-T is Benign according to our data. Variant chr11-125997158-G-T is described in ClinVar as Benign. ClinVar VariationId is 260786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 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.2362+49C>A		intron	N/A	NP_001365893.1
	CDON	NM_001243597.3		c.2362+49C>A		intron	N/A	NP_001230526.1
	CDON	NM_001441161.1		c.2362+49C>A		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.2362+49C>A		intron	N/A	ENSP00000432901.2
	CDON	ENST00000392693.7	TSL:1	c.2362+49C>A		intron	N/A	ENSP00000376458.3
	CDON	ENST00000263577.11	TSL:1	c.2362+49C>A		intron	N/A	ENSP00000263577.7

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141142 AN: 152042 Hom.: 65553 Cov.: 32

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.918

GnomAD2 exomes AF: 0.931 AC: 229870 AN: 246864 AF XY: 0.930

Gnomad AFR exome AF: 0.925

Gnomad AMR exome AF: 0.962

Gnomad ASJ exome AF: 0.905

Gnomad EAS exome AF: 0.995

Gnomad FIN exome AF: 0.933

Gnomad NFE exome AF: 0.918

Gnomad OTH exome AF: 0.929

GnomAD4 exome AF: 0.925 AC: 1060225 AN: 1145670 Hom.: 490873 Cov.: 16 AF XY: 0.925 AC XY: 541851 AN XY: 585918

African (AFR) AF: 0.925 AC: 25099 AN: 27130

American (AMR) AF: 0.960 AC: 42450 AN: 44236

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 21960 AN: 24180

East Asian (EAS) AF: 0.998 AC: 38036 AN: 38104

South Asian (SAS) AF: 0.918 AC: 73022 AN: 79560

European-Finnish (FIN) AF: 0.930 AC: 49374 AN: 53084

Middle Eastern (MID) AF: 0.889 AC: 4611 AN: 5184

European-Non Finnish (NFE) AF: 0.921 AC: 759426 AN: 824192

Other (OTH) AF: 0.925 AC: 46247 AN: 50000

GnomAD4 genome AF: 0.928 AC: 141266 AN: 152160 Hom.: 65617 Cov.: 32 AF XY: 0.929 AC XY: 69123 AN XY: 74396

African (AFR) AF: 0.927 AC: 38455 AN: 41500

American (AMR) AF: 0.947 AC: 14476 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3148 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5141 AN: 5168

South Asian (SAS) AF: 0.919 AC: 4428 AN: 4818

European-Finnish (FIN) AF: 0.937 AC: 9922 AN: 10594

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62607 AN: 68002

Other (OTH) AF: 0.918 AC: 1936 AN: 2108

Alfa AF: 0.909 Hom.: 6540

Bravo AF: 0.930

Asia WGS AF: 0.958 AC: 3334 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Holoprosencephaly 11 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.35
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11220309; hg19: chr11-125867053;