11-125994431-T-C

Variant names:

• chr11-125994431-T-C
• rs2155355
• NM_001378964.1:c.2545-42A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378964.1(CDON):​c.2545-42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,065,142 control chromosomes in the GnomAD database, including 50,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (6946 hom., cov: 32)
  • Exomes 𝑓: 0.31 (43146 hom.)
• Consequence: CDON NM_001378964.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0560
• Publications: 8 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]

CDON Gene-Disease associations (from GenCC):

• holoprosencephaly 11

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-125994431-T-C is Benign according to our data. Variant chr11-125994431-T-C is described in ClinVar as Benign. ClinVar VariationId is 260788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDON	NM_001378964.1	c.2545-42A>G		intron_variant	Intron 13 of 19	ENST00000531738.6	NP_001365893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDON	ENST00000531738.6	c.2545-42A>G		intron_variant	Intron 13 of 19	1	NM_001378964.1	ENSP00000432901.2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45655 AN: 151976 Hom.: 6931 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.283

GnomAD2 exomes AF: 0.313 AC: 72317 AN: 230896 AF XY: 0.316

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.281

Gnomad FIN exome AF: 0.369

Gnomad NFE exome AF: 0.300

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.308 AC: 280810 AN: 913048 Hom.: 43146 Cov.: 12 AF XY: 0.309 AC XY: 147218 AN XY: 477106

African (AFR) AF: 0.300 AC: 6829 AN: 22766

American (AMR) AF: 0.300 AC: 12786 AN: 42676

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 7987 AN: 22662

East Asian (EAS) AF: 0.276 AC: 10173 AN: 36870

South Asian (SAS) AF: 0.343 AC: 25450 AN: 74114

European-Finnish (FIN) AF: 0.357 AC: 18627 AN: 52234

Middle Eastern (MID) AF: 0.283 AC: 1333 AN: 4712

European-Non Finnish (NFE) AF: 0.300 AC: 184340 AN: 614882

Other (OTH) AF: 0.315 AC: 13285 AN: 42132

GnomAD4 genome AF: 0.301 AC: 45713 AN: 152094 Hom.: 6946 Cov.: 32 AF XY: 0.303 AC XY: 22544 AN XY: 74332

African (AFR) AF: 0.293 AC: 12148 AN: 41496

American (AMR) AF: 0.296 AC: 4531 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3472

East Asian (EAS) AF: 0.288 AC: 1487 AN: 5172

South Asian (SAS) AF: 0.337 AC: 1626 AN: 4820

European-Finnish (FIN) AF: 0.369 AC: 3893 AN: 10550

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19921 AN: 67986

Other (OTH) AF: 0.282 AC: 596 AN: 2110

Alfa AF: 0.300 Hom.: 3994

Bravo AF: 0.297

Asia WGS AF: 0.304 AC: 1057 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		0.056
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2155355; hg19: chr11-125864326; COSMIC: COSV107221590;