rs12607660

Positions:

• chr18-52596419-T-C

Variant summary

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

The NM_005215.4(DCC):​c.92-155635T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,986 control chromosomes in the GnomAD database, including 20,035 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 0.51 (20035 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCC	NM_005215.4	c.92-155635T>C		intron_variant		ENST00000442544.7
DCC	XM_017025568.2	c.92-155635T>C		intron_variant
DCC	XM_017025569.2	c.92-155635T>C		intron_variant
DCC	XM_047437311.1	c.92-155635T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCC	ENST00000442544.7	c.92-155635T>C		intron_variant		1	NM_005215.4	P1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77006 AN: 151870 Hom.: 20013 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.507 AC: 77082 AN: 151986 Hom.: 20035 Cov.: 32 AF XY: 0.506 AC XY: 37602 AN XY: 74270

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.506

Alfa AF: 0.531 Hom.: 5364

Bravo AF: 0.496

Asia WGS AF: 0.366 AC: 1271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.87
DANN	Benign	0.26

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: rs12607660; hg19: chr18-50122789;