rs9965768

chr18-52603667-T-Achr18-52603667-T-G

Variant summary

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

The NM_005215.4(DCC):c.92-148387T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 150,888 control chromosomes in the GnomAD database, including 11,511 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 0.39 (11511 hom., cov: 29)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCC	NM_005215.4	c.92-148387T>A		intron_variant		ENST00000442544.7
DCC	XM_017025568.2	c.92-148387T>A		intron_variant
DCC	XM_017025569.2	c.92-148387T>A		intron_variant
DCC	XM_047437311.1	c.92-148387T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCC	ENST00000442544.7	c.92-148387T>A		intron_variant		1	NM_005215.4	P1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58714 AN: 150774 Hom.: 11504 Cov.: 29

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.389 AC: 58730 AN: 150888 Hom.: 11511 Cov.: 29 AF XY: 0.384 AC XY: 28300 AN XY: 73702

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.411

Alfa AF: 0.394 Hom.: 1481

Bravo AF: 0.394

Asia WGS AF: 0.367 AC: 1274 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.2
Dann	Benign	0.80

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: rs9965768; hg19: chr18-50130037;