11-125957023-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001378964.1(CDON):c.*3919T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 238,100 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (3 hom.)
• Consequence: CDON NM_001378964.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0110

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=-0.85).
• BP6: Variant 11-125957023-A-G is Benign according to our data. Variant chr11-125957023-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 303376.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00377 (574/152326) while in subpopulation NFE AF= 0.00422 (287/68028). AF 95% confidence interval is 0.00382. There are 3 homozygotes in gnomad4. There are 271 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 575 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDON	NM_001378964.1	c.*3919T>C		3_prime_UTR_variant	20/20	ENST00000531738.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDON	ENST00000531738.6	c.*3919T>C		3_prime_UTR_variant	20/20	1	NM_001378964.1	P1
CDON	ENST00000392693.7	c.*3919T>C		3_prime_UTR_variant	20/20	1
VSIG10L2	ENST00000638636.2	c.*1109A>G		3_prime_UTR_variant	10/10	5		A2
CDON	ENST00000684078.1	c.*3919T>C		3_prime_UTR_variant	20/20

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 575 AN: 152208 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00423

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00315 AC: 270 AN: 85774 Hom.: 3 Cov.: 5 AF XY: 0.00324 AC XY: 134 AN XY: 41338

Gnomad4 AFR exome AF: 0.00205

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.0370

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00293

Gnomad4 OTH exome AF: 0.00522

GnomAD4 genome AF: 0.00377 AC: 574 AN: 152326 Hom.: 3 Cov.: 33 AF XY: 0.00364 AC XY: 271 AN XY: 74486

Gnomad4 AFR AF: 0.000625

Gnomad4 AMR AF: 0.00418

Gnomad4 ASJ AF: 0.0423

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.00422

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00482 Hom.: 3

Bravo AF: 0.00400

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Holoprosencephaly 11 Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.1
Dann	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61917811; hg19: chr11-125826918;