chr11-125957058-A-C

Position:

• chr11-125957058-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378964.1(CDON):​c.*3884T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 164,026 control chromosomes in the GnomAD database, including 7,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7034 hom., cov: 32)
  • Exomes 𝑓: 0.27 (460 hom.)
• Consequence: CDON NM_001378964.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.519

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=-0.85).
• BP6: Variant 11-125957058-A-C is Benign according to our data. Variant chr11-125957058-A-C is described in ClinVar as [Benign]. Clinvar id is 303378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1	c.*3884T>G		3_prime_UTR_variant	20/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6	c.*3884T>G		3_prime_UTR_variant	20/20	1	NM_001378964.1	P1
CDON	ENST00000392693.7	c.*3884T>G		3_prime_UTR_variant	20/20	1
VSIG10L2	ENST00000638636.2	c.*1144A>C		3_prime_UTR_variant	10/10	5		A2
CDON	ENST00000684078.1	c.*3884T>G		3_prime_UTR_variant	20/20

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44685 AN: 151954 Hom.: 7023 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.270 AC: 3233 AN: 11954 Hom.: 460 Cov.: 4 AF XY: 0.274 AC XY: 1606 AN XY: 5860

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.400

Gnomad4 ASJ exome AF: 0.304

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.294 AC: 44727 AN: 152072 Hom.: 7034 Cov.: 32 AF XY: 0.297 AC XY: 22043 AN XY: 74314

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.286

Alfa AF: 0.320 Hom.: 2187

Bravo AF: 0.284

Asia WGS AF: 0.293 AC: 1019 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	-0.85
CADD	Benign	4.2
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13424; hg19: chr11-125826953;