NM_001378964.1:c.1671G>A

Variant names:

• chr11-126005939-C-T
• rs35884952
• NM_001378964.1:c.1671G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001378964.1(CDON):​c.1671G>A​(p.Lys557Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,614,058 control chromosomes in the GnomAD database, including 468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (33 hom., cov: 32)
  • Exomes 𝑓: 0.023 (435 hom.)
• Consequence: CDON NM_001378964.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0280
• Publications: 3 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: Illumina, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pituitary stalk interruption syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.036).
• BP6: Variant 11-126005939-C-T is Benign according to our data. Variant chr11-126005939-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.028 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.017 (2586/152212) while in subpopulation NFE AF = 0.0263 (1785/67996). AF 95% confidence interval is 0.0252. There are 33 homozygotes in GnomAd4. There are 1235 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2586 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378964.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	NM_001378964.1	MANE Select	c.1671G>A	p.Lys557Lys	synonymous	Exon 9 of 20	NP_001365893.1	Q4KMG0-2
	CDON	NM_001243597.3		c.1671G>A	p.Lys557Lys	synonymous	Exon 9 of 20	NP_001230526.1
	CDON	NM_001441161.1		c.1671G>A	p.Lys557Lys	synonymous	Exon 9 of 20	NP_001428090.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDON	ENST00000531738.6	TSL:1 MANE Select	c.1671G>A	p.Lys557Lys	synonymous	Exon 9 of 20	ENSP00000432901.2	Q4KMG0-2
	CDON	ENST00000392693.7	TSL:1	c.1671G>A	p.Lys557Lys	synonymous	Exon 9 of 20	ENSP00000376458.3	Q4KMG0-1
	CDON	ENST00000263577.11	TSL:1	c.1671G>A	p.Lys557Lys	synonymous	Exon 9 of 20	ENSP00000263577.7	Q4KMG0-2

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2586 AN: 152094 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00406

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.0181 AC: 4544 AN: 251110 AF XY: 0.0182

Gnomad AFR exome AF: 0.00400

Gnomad AMR exome AF: 0.00954

Gnomad ASJ exome AF: 0.0156

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0315

Gnomad NFE exome AF: 0.0266

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0229 AC: 33517 AN: 1461846 Hom.: 435 Cov.: 32 AF XY: 0.0223 AC XY: 16231 AN XY: 727230

African (AFR) AF: 0.00338 AC: 113 AN: 33480

American (AMR) AF: 0.00937 AC: 419 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0168 AC: 439 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00636 AC: 549 AN: 86258

European-Finnish (FIN) AF: 0.0322 AC: 1722 AN: 53420

Middle Eastern (MID) AF: 0.00641 AC: 37 AN: 5768

European-Non Finnish (NFE) AF: 0.0261 AC: 29037 AN: 1111970

Other (OTH) AF: 0.0199 AC: 1201 AN: 60394

GnomAD4 genome AF: 0.0170 AC: 2586 AN: 152212 Hom.: 33 Cov.: 32 AF XY: 0.0166 AC XY: 1235 AN XY: 74448

African (AFR) AF: 0.00404 AC: 168 AN: 41542

American (AMR) AF: 0.00994 AC: 152 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00498 AC: 24 AN: 4822

European-Finnish (FIN) AF: 0.0326 AC: 346 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0263 AC: 1785 AN: 67996

Other (OTH) AF: 0.0152 AC: 32 AN: 2108

Alfa AF: 0.0236 Hom.: 67

Bravo AF: 0.0151

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0234

EpiControl AF: 0.0247

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Holoprosencephaly 11 (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.1
DANN	Benign	0.46
PhyloP100		0.028
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: rs35884952; hg19: chr11-125875834; COSMIC: COSV54994958; COSMIC: COSV54994958;