rs11082983

Positions:

• chr18-53377457-A-G

Variant summary

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

The NM_005215.4(DCC):​c.2360-8586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 151,728 control chromosomes in the GnomAD database, including 2,431 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 (2431 hom., cov: 31)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCC	NM_005215.4	c.2360-8586A>G		intron_variant		ENST00000442544.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCC	ENST00000442544.7	c.2360-8586A>G		intron_variant		1	NM_005215.4	P1
DCC	ENST00000581580.5	c.1325-8586A>G		intron_variant		1
DCC	ENST00000304775.12	c.2161-8586A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24353 AN: 151608 Hom.: 2426 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0771

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.161 AC: 24371 AN: 151728 Hom.: 2431 Cov.: 31 AF XY: 0.163 AC XY: 12114 AN XY: 74142

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0771

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.150

Alfa AF: 0.118 Hom.: 579

Bravo AF: 0.159

Asia WGS AF: 0.190 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.8
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: rs11082983; hg19: chr18-50903827;