rs1502222

Variant names:

• chr18-53497197-C-T
• rs1502222
• NM_005215.4:c.3899-2101C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005215.4(DCC):​c.3899-2101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 152,164 control chromosomes in the GnomAD database, including 1,261 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 0.079 (1261 hom., cov: 33)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460
• Publications: 2 publications found

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]

LINC01917 (HGNC:52736): (long intergenic non-protein coding RNA 1917)

LOC124904304 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCC	NM_005215.4	c.3899-2101C>T		intron_variant	Intron 26 of 28	ENST00000442544.7	NP_005206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.3899-2101C>T		intron_variant	Intron 26 of 28	1	NM_005215.4	ENSP00000389140.2

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12042 AN: 152046 Hom.: 1258 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0337

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.0687

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.00396

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0657

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

GnomAD4 genome AF: 0.0792 AC: 12054 AN: 152164 Hom.: 1261 Cov.: 33 AF XY: 0.0772 AC XY: 5746 AN XY: 74382

African (AFR) AF: 0.241 AC: 10003 AN: 41492

American (AMR) AF: 0.0337 AC: 515 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3462

East Asian (EAS) AF: 0.0689 AC: 356 AN: 5168

South Asian (SAS) AF: 0.0357 AC: 172 AN: 4824

European-Finnish (FIN) AF: 0.00396 AC: 42 AN: 10602

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 765 AN: 68010

Other (OTH) AF: 0.0650 AC: 137 AN: 2108

Alfa AF: 0.0440 Hom.: 923

Bravo AF: 0.0883

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.2
DANN	Benign	0.38
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1502222; hg19: chr18-51023567;