11-125956862-C-T

Position:

• chr11-125956862-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378964.1(CDON):​c.*4080G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 985,742 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (149 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (65 hom.)
• Consequence: CDON NM_001378964.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.653

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-125956862-C-T is Benign according to our data. Variant chr11-125956862-C-T is described in ClinVar as [Benign]. Clinvar id is 303373.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDON	NM_001378964.1	c.*4080G>A		3_prime_UTR_variant	20/20	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6	c.*4080G>A		3_prime_UTR_variant	20/20	1	NM_001378964.1	ENSP00000432901	P1
CDON	ENST00000392693.7	c.*4080G>A		3_prime_UTR_variant	20/20	1		ENSP00000376458
VSIG10L2	ENST00000638636.2	c.*948C>T		3_prime_UTR_variant	10/10	5		ENSP00000491467	A2
CDON	ENST00000684078.1	c.*4080G>A		3_prime_UTR_variant	20/20			ENSP00000507318

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3501 AN: 152046 Hom.: 148 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00185 AC: 1540 AN: 833578 Hom.: 65 Cov.: 29 AF XY: 0.00167 AC XY: 642 AN XY: 384996

Gnomad4 AFR exome AF: 0.0844

Gnomad4 AMR exome AF: 0.00283

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000127

Gnomad4 OTH exome AF: 0.00359

GnomAD4 genome AF: 0.0231 AC: 3512 AN: 152164 Hom.: 149 Cov.: 32 AF XY: 0.0219 AC XY: 1631 AN XY: 74400

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.00909

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0111 Hom.: 10

Bravo AF: 0.0264

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.78
CADD	Benign	7.8
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs79685272; hg19: chr11-125826757;