11-125956942-G-A

Variant names:

• chr11-125956942-G-A
• rs79719160
• NM_001378964.1:c.*4000C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001378964.1(CDON):​c.*4000C>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 0.000381 in 810,690 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: CDON NM_001378964.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.300
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-125956942-G-A is Benign according to our data. Variant chr11-125956942-G-A is described in ClinVar as [Benign]. Clinvar id is 878588.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 216 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.*4000C>T		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.*4000C>T		3_prime_UTR_variant	Exon 20 of 20	1	NM_001378964.1	ENSP00000432901.2
CDON	ENST00000392693.7	c.*4000C>T		3_prime_UTR_variant	Exon 20 of 20	1		ENSP00000376458.3
CDON	ENST00000684078.1	c.*4000C>T		3_prime_UTR_variant	Exon 20 of 20			ENSP00000507318.1
VSIG10L2	ENST00000638636.2	c.*1028G>A		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000491467.1

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 216 AN: 152084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000141 AC: 93 AN: 658488 Hom.: 1 Cov.: 8 AF XY: 0.000166 AC XY: 51 AN XY: 307162

African (AFR) AF: 0.00721 AC: 89 AN: 12344

American (AMR) AF: 0.00 AC: 0 AN: 794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4010

East Asian (EAS) AF: 0.00 AC: 0 AN: 2776

South Asian (SAS) AF: 0.00 AC: 0 AN: 13040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 602500

Other (OTH) AF: 0.000186 AC: 4 AN: 21528

GnomAD4 genome AF: 0.00142 AC: 216 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.00132 AC XY: 98 AN XY: 74412

African (AFR) AF: 0.00513 AC: 213 AN: 41520

American (AMR) AF: 0.000196 AC: 3 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00160 Hom.: 0

Bravo AF: 0.00167

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: 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: 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 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	0.92
DANN	Benign	0.72
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs79719160; hg19: chr11-125826837;