11-125957023-A-G

Variant names:

• chr11-125957023-A-G
• rs61917811
• NM_001378964.1:c.*3919T>C

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.*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
• 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 11-125957023-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.
• BS2: High AC in GnomAd4 at 574 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.*3919T>C		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.*3919T>C		3_prime_UTR_variant	Exon 20 of 20	1	NM_001378964.1	ENSP00000432901.2

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

African (AFR) AF: 0.00205 AC: 3 AN: 1466

American (AMR) AF: 0.0114 AC: 1 AN: 88

Ashkenazi Jewish (ASJ) AF: 0.0370 AC: 18 AN: 486

East Asian (EAS) AF: 0.00 AC: 0 AN: 340

South Asian (SAS) AF: 0.00121 AC: 2 AN: 1656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26

Middle Eastern (MID) AF: 0.00562 AC: 1 AN: 178

European-Non Finnish (NFE) AF: 0.00293 AC: 231 AN: 78852

Other (OTH) AF: 0.00522 AC: 14 AN: 2682

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

African (AFR) AF: 0.000625 AC: 26 AN: 41574

American (AMR) AF: 0.00418 AC: 64 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 147 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00422 AC: 287 AN: 68028

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

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

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	-0.85
CADD	Benign	4.1
DANN	Benign	0.54
PhyloP100		-0.011
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: rs61917811; hg19: chr11-125826918;