18-52666026-C-T

Position:

• chr18-52666026-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005215.4(DCC):​c.92-86028C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,996 control chromosomes in the GnomAD database, including 11,043 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 0.38 (11043 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCC	NM_005215.4	c.92-86028C>T		intron_variant		ENST00000442544.7	NP_005206.2
DCC	XM_017025568.2	c.92-86028C>T		intron_variant			XP_016881057.1
DCC	XM_017025569.2	c.92-86028C>T		intron_variant			XP_016881058.1
DCC	XM_047437311.1	c.92-86028C>T		intron_variant			XP_047293267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.92-86028C>T		intron_variant		1	NM_005215.4	ENSP00000389140.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57504 AN: 151878 Hom.: 11036 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.378 AC: 57524 AN: 151996 Hom.: 11043 Cov.: 32 AF XY: 0.378 AC XY: 28068 AN XY: 74288

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.351

Alfa AF: 0.384 Hom.: 7429

Bravo AF: 0.372

Asia WGS AF: 0.342 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs4940203; hg19: chr18-50192396;