rs768048

Positions:

• chr18-52759028-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.412+6654C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 151,940 control chromosomes in the GnomAD database, including 4,780 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 0.21 (4780 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCC	NM_005215.4	c.412+6654C>T		intron_variant		ENST00000442544.7
DCC	XM_017025568.2	c.412+6654C>T		intron_variant
DCC	XM_017025569.2	c.412+6654C>T		intron_variant
DCC	XM_047437311.1	c.412+6654C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCC	ENST00000442544.7	c.412+6654C>T		intron_variant		1	NM_005215.4	P1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31864 AN: 151822 Hom.: 4765 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0725

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.219

GnomAD3 exomes AF: 0.500 AC: 1 AN: 2 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad NFE exome AF: 0.500

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.210 AC: 31911 AN: 151940 Hom.: 4780 Cov.: 32 AF XY: 0.204 AC XY: 15116 AN XY: 74272

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0725

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.215

Alfa AF: 0.147 Hom.: 3047

Bravo AF: 0.224

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.48

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: rs768048; hg19: chr18-50285398;