rs17468382

Positions:

• chr18-52734641-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005215.4(DCC):​c.92-17413T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 152,206 control chromosomes in the GnomAD database, including 134 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 0.036 (134 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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=-0.86).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0364 (5537/152206) while in subpopulation AMR AF= 0.0488 (746/15274). AF 95% confidence interval is 0.0461. There are 134 homozygotes in gnomad4. There are 2796 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 134 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCC	NM_005215.4	c.92-17413T>C		intron_variant		ENST00000442544.7	NP_005206.2
DCC	XM_017025568.2	c.92-17413T>C		intron_variant			XP_016881057.1
DCC	XM_017025569.2	c.92-17413T>C		intron_variant			XP_016881058.1
DCC	XM_047437311.1	c.92-17413T>C		intron_variant			XP_047293267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.92-17413T>C		intron_variant		1	NM_005215.4	ENSP00000389140.2

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5537 AN: 152088 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.0366

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0475

Gnomad OTH AF: 0.0321

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

GnomAD4 genome AF: 0.0364 AC: 5537 AN: 152206 Hom.: 134 Cov.: 32 AF XY: 0.0376 AC XY: 2796 AN XY: 74412

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.0488

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.0367

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.0475

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0410 Hom.: 20

Bravo AF: 0.0342

Asia WGS AF: 0.0450 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.77

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: rs17468382; hg19: chr18-50261011;