18-53451428-A-G

Position:

• chr18-53451428-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.3392+766A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,020 control chromosomes in the GnomAD database, including 18,966 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 0.49 (18966 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCC	NM_005215.4	c.3392+766A>G		intron_variant		ENST00000442544.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCC	ENST00000442544.7	c.3392+766A>G		intron_variant		1	NM_005215.4	P1
DCC	ENST00000581580.5	c.2297+766A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73853 AN: 151902 Hom.: 18954 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.486 AC: 73875 AN: 152020 Hom.: 18966 Cov.: 32 AF XY: 0.484 AC XY: 35994 AN XY: 74306

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.494

Alfa AF: 0.552 Hom.: 18178

Bravo AF: 0.460

Asia WGS AF: 0.344 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.68

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: rs869224; hg19: chr18-50977798;