18-52684510-C-T

Position:

• chr18-52684510-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
DCC	NM_005215.4	c.92-67544C>T		intron_variant		ENST00000442544.7
DCC	XM_017025568.2	c.92-67544C>T		intron_variant
DCC	XM_017025569.2	c.92-67544C>T		intron_variant
DCC	XM_047437311.1	c.92-67544C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCC	ENST00000442544.7	c.92-67544C>T		intron_variant		1	NM_005215.4	P1

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

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.407

Alfa AF: 0.455 Hom.: 33145

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

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: rs12962177; hg19: chr18-50210880;