rs1221862

Variant names:

• chr18-52617389-T-C
• rs1221862
• NM_005215.4:c.92-134665T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-52617389-T-C
• chr18-52617389-T-G

Variant summary

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

The NM_005215.4(DCC):​c.92-134665T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,964 control chromosomes in the GnomAD database, including 12,790 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 0.41 (12790 hom., cov: 31)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.642
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 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.92-134665T>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.92-134665T>C		intron	N/A	ENSP00000389140.2	P43146

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61948 AN: 151846 Hom.: 12779 Cov.: 31

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.408 AC: 61981 AN: 151964 Hom.: 12790 Cov.: 31 AF XY: 0.403 AC XY: 29950 AN XY: 74258

African (AFR) AF: 0.368 AC: 15254 AN: 41446

American (AMR) AF: 0.377 AC: 5750 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1557 AN: 3468

East Asian (EAS) AF: 0.380 AC: 1957 AN: 5148

South Asian (SAS) AF: 0.395 AC: 1906 AN: 4820

European-Finnish (FIN) AF: 0.381 AC: 4018 AN: 10554

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.441 AC: 30001 AN: 67964

Other (OTH) AF: 0.425 AC: 895 AN: 2108

Alfa AF: 0.432 Hom.: 1899

Bravo AF: 0.404

Asia WGS AF: 0.380 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.60
PhyloP100		0.64
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: rs1221862; hg19: chr18-50143759;