rs997489

Positions:

• chr18-52604153-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.92-147901C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 152,094 control chromosomes in the GnomAD database, including 102 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 0.020 (102 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCC	NM_005215.4	c.92-147901C>T		intron_variant		ENST00000442544.7
DCC	XM_017025568.2	c.92-147901C>T		intron_variant
DCC	XM_017025569.2	c.92-147901C>T		intron_variant
DCC	XM_047437311.1	c.92-147901C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCC	ENST00000442544.7	c.92-147901C>T		intron_variant		1	NM_005215.4	P1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 3012 AN: 151976 Hom.: 100 Cov.: 32

Gnomad AFR AF: 0.00377

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0651

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0901

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00929

Gnomad OTH AF: 0.0220

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

GnomAD4 genome AF: 0.0199 AC: 3020 AN: 152094 Hom.: 102 Cov.: 32 AF XY: 0.0227 AC XY: 1688 AN XY: 74328

Gnomad4 AFR AF: 0.00376

Gnomad4 AMR AF: 0.0655

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.0905

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.0461

Gnomad4 NFE AF: 0.00929

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.0168 Hom.: 8

Bravo AF: 0.0230

Asia WGS AF: 0.0510 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.84

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: rs997489; hg19: chr18-50130523;