18-52684510-C-T

Variant names:

• chr18-52684510-C-T
• rs12962177
• NM_005215.4:c.92-67544C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005215.4(DCC):​c.92-67544C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,718 control chromosomes in the GnomAD database, including 12,915 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 (12915 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 4 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), Illumina, Ambry Genetics
• 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: G2P, Ambry Genetics
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCC	NM_005215.4	c.92-67544C>T		intron_variant	Intron 1 of 28	ENST00000442544.7	NP_005206.2
DCC	XM_017025568.2	c.92-67544C>T		intron_variant	Intron 1 of 28		XP_016881057.1
DCC	XM_017025569.2	c.92-67544C>T		intron_variant	Intron 1 of 28		XP_016881058.1
DCC	XM_047437311.1	c.92-67544C>T		intron_variant	Intron 1 of 28		XP_047293267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.92-67544C>T		intron_variant	Intron 1 of 28	1	NM_005215.4	ENSP00000389140.2

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61655 AN: 151600 Hom.: 12909 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.407 AC: 61684 AN: 151718 Hom.: 12915 Cov.: 32 AF XY: 0.402 AC XY: 29779 AN XY: 74122

African (AFR) AF: 0.307 AC: 12710 AN: 41378

American (AMR) AF: 0.424 AC: 6440 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1363 AN: 3468

East Asian (EAS) AF: 0.376 AC: 1939 AN: 5158

South Asian (SAS) AF: 0.289 AC: 1389 AN: 4810

European-Finnish (FIN) AF: 0.426 AC: 4460 AN: 10474

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32166 AN: 67920

Other (OTH) AF: 0.407 AC: 856 AN: 2104

Alfa AF: 0.448 Hom.: 47861

Bravo AF: 0.401

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.60
PhyloP100		2.1
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: rs12962177; hg19: chr18-50210880;