chr11-125957080-C-A

Position:

• chr11-125957080-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001378964.1(CDON):​c.*3862G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 155,738 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (139 hom., cov: 32)
  • Exomes 𝑓: 0.025 (0 hom.)
• Consequence: CDON NM_001378964.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.321

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]

VSIG10L2 (HGNC:27879): (V-set and immunoglobulin domain containing 10 like 2) Predicted to enable cell adhesion molecule binding activity. Predicted to be involved in cell-cell adhesion. Predicted to be active in cell-cell junction. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-125957080-C-A is Benign according to our data. Variant chr11-125957080-C-A is described in ClinVar as [Benign]. Clinvar id is 303379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0368 (5598/152212) while in subpopulation AFR AF= 0.0475 (1972/41508). AF 95% confidence interval is 0.0458. There are 139 homozygotes in gnomad4. There are 2783 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5598 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1	c.*3862G>T		3_prime_UTR_variant	20/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6	c.*3862G>T		3_prime_UTR_variant	20/20	1	NM_001378964.1	P1
CDON	ENST00000392693.7	c.*3862G>T		3_prime_UTR_variant	20/20	1
VSIG10L2	ENST00000638636.2	c.*1166C>A		3_prime_UTR_variant	10/10	5		A2
CDON	ENST00000684078.1	c.*3862G>T		3_prime_UTR_variant	20/20

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5573 AN: 152094 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0831

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0345

GnomAD4 exome AF: 0.0250 AC: 88 AN: 3526 Hom.: 0 Cov.: 3 AF XY: 0.0205 AC XY: 37 AN XY: 1804

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0417

Gnomad4 EAS exome AF: 0.0500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0257

Gnomad4 OTH exome AF: 0.0185

GnomAD4 genome AF: 0.0368 AC: 5598 AN: 152212 Hom.: 139 Cov.: 32 AF XY: 0.0374 AC XY: 2783 AN XY: 74404

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.00656

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.0831

Gnomad4 NFE AF: 0.0286

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0197 Hom.: 10

Bravo AF: 0.0331

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Holoprosencephaly 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs73019367; hg19: chr11-125826975;