rs1144093

chr18-52590710-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.92-161344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,138 control chromosomes in the GnomAD database, including 4,598 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 0.24 (4598 hom., cov: 33)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCC	NM_005215.4	c.92-161344C>T		intron_variant		ENST00000442544.7
DCC	XM_017025568.2	c.92-161344C>T		intron_variant
DCC	XM_017025569.2	c.92-161344C>T		intron_variant
DCC	XM_047437311.1	c.92-161344C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCC	ENST00000442544.7	c.92-161344C>T		intron_variant		1	NM_005215.4	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36897 AN: 152020 Hom.: 4594 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.243 AC: 36922 AN: 152138 Hom.: 4598 Cov.: 33 AF XY: 0.236 AC XY: 17539 AN XY: 74376

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.257

Alfa AF: 0.250 Hom.: 842

Bravo AF: 0.250

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.84
Dann	Benign	0.71

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: rs1144093; hg19: chr18-50117080;