11-125956970-G-C

Variant names:

• chr11-125956970-G-C
• rs142923654
• NM_001378964.1:c.*3972C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001378964.1(CDON):​c.*3972C>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 0.00855 in 622,258 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0068 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0091 (22 hom.)
• Consequence: CDON NM_001378964.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.318
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High AC in GnomAd4 at 1041 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.*3972C>G		3_prime_UTR_variant	Exon 20 of 20	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6	c.*3972C>G		3_prime_UTR_variant	Exon 20 of 20	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.00684 AC: 1041 AN: 152228 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00916

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00631

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00911 AC: 4281 AN: 469912 Hom.: 22 Cov.: 6 AF XY: 0.00954 AC XY: 2106 AN XY: 220840

African (AFR) AF: 0.00185 AC: 16 AN: 8672

American (AMR) AF: 0.00180 AC: 1 AN: 556

Ashkenazi Jewish (ASJ) AF: 0.00603 AC: 17 AN: 2818

East Asian (EAS) AF: 0.00 AC: 0 AN: 1876

South Asian (SAS) AF: 0.00130 AC: 12 AN: 9234

European-Finnish (FIN) AF: 0.00667 AC: 1 AN: 150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 938

European-Non Finnish (NFE) AF: 0.00956 AC: 4115 AN: 430374

Other (OTH) AF: 0.00778 AC: 119 AN: 15294

GnomAD4 genome AF: 0.00683 AC: 1041 AN: 152346 Hom.: 8 Cov.: 33 AF XY: 0.00671 AC XY: 500 AN XY: 74500

African (AFR) AF: 0.00185 AC: 77 AN: 41588

American (AMR) AF: 0.00915 AC: 140 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.00631 AC: 67 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0105 AC: 716 AN: 68026

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00576 Hom.: 1

Bravo AF: 0.00650

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Holoprosencephaly 11 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.82
CADD	Benign	0.84
DANN	Benign	0.61
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs142923654; hg19: chr11-125826865;