18-53337438-T-C

Position:

• chr18-53337438-T-C

Variant summary

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

The NM_005215.4(DCC):​c.2165-2275T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,158 control chromosomes in the GnomAD database, including 9,982 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 0.34 (9982 hom., cov: 33)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCC	NM_005215.4	c.2165-2275T>C		intron_variant		ENST00000442544.7	NP_005206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.2165-2275T>C		intron_variant		1	NM_005215.4	ENSP00000389140.2
DCC	ENST00000581580.5	c.1130-2275T>C		intron_variant		1		ENSP00000464582.1
DCC	ENST00000304775.12	n.1964-2275T>C		intron_variant		1		ENSP00000304146.8

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51759 AN: 152040 Hom.: 9969 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.340 AC: 51792 AN: 152158 Hom.: 9982 Cov.: 33 AF XY: 0.348 AC XY: 25870 AN XY: 74362

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.348

Alfa AF: 0.370 Hom.: 10750

Bravo AF: 0.347

Asia WGS AF: 0.535 AC: 1858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.59

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: rs9950970; hg19: chr18-50863808;