chr18-53379661-G-A

Position:

• chr18-53379661-G-A

Variant summary

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

The ENST00000442544.7(DCC):​c.2360-6382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,976 control chromosomes in the GnomAD database, including 16,915 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 0.46 (16915 hom., cov: 32)
• Consequence: DCC ENST00000442544.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

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 = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCC	NM_005215.4	c.2360-6382G>A		intron_variant		ENST00000442544.7	NP_005206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.2360-6382G>A		intron_variant		1	NM_005215.4	ENSP00000389140	P1
DCC	ENST00000581580.5	c.1325-6382G>A		intron_variant		1		ENSP00000464582
DCC	ENST00000304775.12	c.2161-6382G>A		intron_variant, NMD_transcript_variant		1		ENSP00000304146

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69657 AN: 151858 Hom.: 16910 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.458 AC: 69670 AN: 151976 Hom.: 16915 Cov.: 32 AF XY: 0.454 AC XY: 33703 AN XY: 74256

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.465

Alfa AF: 0.484 Hom.: 3138

Bravo AF: 0.436

Asia WGS AF: 0.312 AC: 1086 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	0.89
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: rs11876941; hg19: chr18-50906031;