chr18-53338298-T-G

Variant names:

• chr18-53338298-T-G
• rs1367634
• NM_005215.4:c.2165-1415T>G

Variant summary

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

The NM_005215.4(DCC):​c.2165-1415T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,076 control chromosomes in the GnomAD database, including 29,857 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 (29857 hom., cov: 33)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 5 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]

DCC Gene-Disease associations (from GenCC):

• mirror movements 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• mirror movements 1 and/or agenesis of the corpus callosum

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• gaze palsy, familial horizontal, with progressive scoliosis, 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics
• connective tissue disorder

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• familial congenital mirror movements

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• colorectal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)
• esophageal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• 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 rank	MANE	Protein	UniProt
DCC	NM_005215.4	c.2165-1415T>G		intron_variant	Intron 14 of 28	ENST00000442544.7	NP_005206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.2165-1415T>G		intron_variant	Intron 14 of 28	1	NM_005215.4	ENSP00000389140.2
DCC	ENST00000581580.5	c.1130-1415T>G		intron_variant	Intron 11 of 26	1		ENSP00000464582.1
DCC	ENST00000304775.12	n.1964-1415T>G		intron_variant	Intron 13 of 18	1		ENSP00000304146.8

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94301 AN: 151956 Hom.: 29820 Cov.: 33

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.621 AC: 94384 AN: 152076 Hom.: 29857 Cov.: 33 AF XY: 0.615 AC XY: 45705 AN XY: 74328

African (AFR) AF: 0.679 AC: 28152 AN: 41488

American (AMR) AF: 0.488 AC: 7453 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1859 AN: 3468

East Asian (EAS) AF: 0.417 AC: 2161 AN: 5178

South Asian (SAS) AF: 0.436 AC: 2101 AN: 4822

European-Finnish (FIN) AF: 0.662 AC: 6998 AN: 10566

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43603 AN: 67972

Other (OTH) AF: 0.625 AC: 1318 AN: 2108

Alfa AF: 0.627 Hom.: 80402

Bravo AF: 0.609

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.59
PhyloP100		-1.8
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: rs1367634; hg19: chr18-50864668;