rs12954274

Positions:

• chr18-53339504-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.2165-209C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,004 control chromosomes in the GnomAD database, including 29,811 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 0.62 (29811 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCC	NM_005215.4	c.2165-209C>T		intron_variant		ENST00000442544.7	NP_005206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.2165-209C>T		intron_variant		1	NM_005215.4	ENSP00000389140	P1
DCC	ENST00000581580.5	c.1130-209C>T		intron_variant		1		ENSP00000464582
DCC	ENST00000304775.12	c.1966-209C>T		intron_variant, NMD_transcript_variant		1		ENSP00000304146

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94188 AN: 151886 Hom.: 29776 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.620 AC: 94269 AN: 152004 Hom.: 29811 Cov.: 32 AF XY: 0.614 AC XY: 45629 AN XY: 74288

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.624

Alfa AF: 0.646 Hom.: 4704

Bravo AF: 0.608

Asia WGS AF: 0.459 AC: 1596 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.6
DANN	Benign	0.70

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: rs12954274; hg19: chr18-50865874;