18-52369739-C-T

Variant names:

• chr18-52369739-C-T
• rs11875845
• NM_005215.4:c.91+28861C>T

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+28861C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 151,866 control chromosomes in the GnomAD database, including 1,010 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 0.11 (1010 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCC	NM_005215.4	c.91+28861C>T		intron_variant	Intron 1 of 28	ENST00000442544.7	NP_005206.2
DCC	XM_017025568.2	c.91+28861C>T		intron_variant	Intron 1 of 28		XP_016881057.1
DCC	XM_017025569.2	c.91+28861C>T		intron_variant	Intron 1 of 28		XP_016881058.1
DCC	XM_047437311.1	c.91+28861C>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.91+28861C>T		intron_variant	Intron 1 of 28	1	NM_005215.4	ENSP00000389140.2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16932 AN: 151748 Hom.: 1010 Cov.: 32

Gnomad AFR AF: 0.0997

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.0818

Gnomad ASJ AF: 0.0984

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.112 AC: 16939 AN: 151866 Hom.: 1010 Cov.: 32 AF XY: 0.110 AC XY: 8194 AN XY: 74210

African (AFR) AF: 0.0999 AC: 4138 AN: 41418

American (AMR) AF: 0.0817 AC: 1249 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0984 AC: 341 AN: 3464

East Asian (EAS) AF: 0.109 AC: 562 AN: 5136

South Asian (SAS) AF: 0.156 AC: 748 AN: 4798

European-Finnish (FIN) AF: 0.0932 AC: 980 AN: 10520

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.124 AC: 8444 AN: 67942

Other (OTH) AF: 0.120 AC: 254 AN: 2108

Alfa AF: 0.122 Hom.: 1659

Bravo AF: 0.109

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.20
PhyloP100		0.13
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: rs11875845; hg19: chr18-49896109;