18-53334162-G-T

Position:

• chr18-53334162-G-T

Variant summary

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

The NM_005215.4(DCC):​c.2165-5551G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,020 control chromosomes in the GnomAD database, including 2,356 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 0.16 (2356 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCC	NM_005215.4	c.2165-5551G>T		intron_variant		ENST00000442544.7	NP_005206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.2165-5551G>T		intron_variant		1	NM_005215.4	ENSP00000389140	P1
DCC	ENST00000581580.5	c.1130-5551G>T		intron_variant		1		ENSP00000464582
DCC	ENST00000304775.12	c.1966-5551G>T		intron_variant, NMD_transcript_variant		1		ENSP00000304146

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24067 AN: 151904 Hom.: 2352 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.158 AC: 24083 AN: 152020 Hom.: 2356 Cov.: 32 AF XY: 0.161 AC XY: 11970 AN XY: 74304

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0712

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.146

Alfa AF: 0.117 Hom.: 565

Bravo AF: 0.157

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.53

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: rs11872471; hg19: chr18-50860532;