18-52352494-G-C

Variant names:

• chr18-52352494-G-C
• rs959655
• NM_005215.4:c.91+11616G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005215.4(DCC):​c.91+11616G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,176 control chromosomes in the GnomAD database, including 55,916 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 0.86 (55916 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659
• Publications: 6 publications found

Genes affected

DCC (HGNC:2701): (DCC netrin 1 receptor) This gene encodes a netrin 1 receptor. The transmembrane protein is a member of the immunoglobulin superfamily of cell adhesion molecules, and mediates axon guidance of neuronal growth cones towards sources of netrin 1 ligand. The cytoplasmic tail interacts with the tyrosine kinases Src and focal adhesion kinase (FAK, also known as PTK2) to mediate axon attraction. The protein partially localizes to lipid rafts, and induces apoptosis in the absence of ligand. The protein functions as a tumor suppressor, and is frequently mutated or downregulated in colorectal cancer and esophageal carcinoma. [provided by RefSeq, Oct 2009]

DCC Gene-Disease associations (from GenCC):

• mirror movements 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina
• mirror movements 1 and/or agenesis of the corpus callosum

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• gaze palsy, familial horizontal, with progressive scoliosis, 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P
• connective tissue disorder

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• familial congenital mirror movements

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• colorectal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)
• esophageal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005215.4. 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
	DCC	NM_005215.4	MANE Select	c.91+11616G>C		intron	N/A	NP_005206.2	P43146

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCC	ENST00000442544.7	TSL:1 MANE Select	c.91+11616G>C		intron	N/A	ENSP00000389140.2	P43146

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130227 AN: 152058 Hom.: 55870 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.855

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.856 AC: 130329 AN: 152176 Hom.: 55916 Cov.: 32 AF XY: 0.853 AC XY: 63458 AN XY: 74382

African (AFR) AF: 0.893 AC: 37105 AN: 41550

American (AMR) AF: 0.871 AC: 13312 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2913 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4483 AN: 5176

South Asian (SAS) AF: 0.830 AC: 4000 AN: 4818

European-Finnish (FIN) AF: 0.790 AC: 8352 AN: 10568

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57289 AN: 67988

Other (OTH) AF: 0.855 AC: 1807 AN: 2114

Alfa AF: 0.811 Hom.: 2485

Bravo AF: 0.867

Asia WGS AF: 0.841 AC: 2924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.68
PhyloP100		-0.66
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: rs959655; hg19: chr18-49878864;