11-125956890-G-A

Position:

• chr11-125956890-G-A

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.*4052C>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 0.303 in 977,810 control chromosomes in the GnomAD database, including 46,021 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5486 hom., cov: 32)
  • Exomes 𝑓: 0.31 (40535 hom.)
• Consequence: CDON NM_001378964.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.561

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=-0.79).
• BP6: Variant 11-125956890-G-A is Benign according to our data. Variant chr11-125956890-G-A is described in ClinVar as [Benign]. Clinvar id is 303374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1	c.*4052C>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.*4052C>T		3_prime_UTR_variant	20/20	1	NM_001378964.1	P1
CDON	ENST00000392693.7	c.*4052C>T		3_prime_UTR_variant	20/20	1
VSIG10L2	ENST00000638636.2	c.*976G>A		3_prime_UTR_variant	10/10	5		A2
CDON	ENST00000684078.1	c.*4052C>T		3_prime_UTR_variant	20/20

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39026 AN: 151874 Hom.: 5482 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.311 AC: 257153 AN: 825816 Hom.: 40535 Cov.: 16 AF XY: 0.312 AC XY: 118891 AN XY: 381604

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.288

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.257 AC: 39045 AN: 151994 Hom.: 5486 Cov.: 32 AF XY: 0.259 AC XY: 19204 AN XY: 74290

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.254

Alfa AF: 0.298 Hom.: 8802

Bravo AF: 0.250

Asia WGS AF: 0.261 AC: 909 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 12, 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	-0.79
CADD	Benign	7.9
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3039; hg19: chr11-125826785;