chr18-53379661-G-A

Variant names:

• chr18-53379661-G-A
• rs11876941
• NM_005215.4:c.2360-6382G>A

Variant summary

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

The NM_005215.4(DCC):​c.2360-6382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,976 control chromosomes in the GnomAD database, including 16,915 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 0.46 (16915 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCC	NM_005215.4	c.2360-6382G>A		intron_variant	Intron 15 of 28	ENST00000442544.7	NP_005206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.2360-6382G>A		intron_variant	Intron 15 of 28	1	NM_005215.4	ENSP00000389140.2
DCC	ENST00000581580.5	c.1325-6382G>A		intron_variant	Intron 12 of 26	1		ENSP00000464582.1
DCC	ENST00000304775.12	n.2159-6382G>A		intron_variant	Intron 14 of 18	1		ENSP00000304146.8

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69657 AN: 151858 Hom.: 16910 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.458 AC: 69670 AN: 151976 Hom.: 16915 Cov.: 32 AF XY: 0.454 AC XY: 33703 AN XY: 74256

African (AFR) AF: 0.368 AC: 15272 AN: 41444

American (AMR) AF: 0.362 AC: 5532 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1431 AN: 3466

East Asian (EAS) AF: 0.248 AC: 1278 AN: 5156

South Asian (SAS) AF: 0.325 AC: 1566 AN: 4822

European-Finnish (FIN) AF: 0.582 AC: 6147 AN: 10564

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36852 AN: 67942

Other (OTH) AF: 0.465 AC: 981 AN: 2108

Alfa AF: 0.447 Hom.: 9317

Bravo AF: 0.436

Asia WGS AF: 0.312 AC: 1086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.89
DANN	Benign	0.59
PhyloP100		-0.18
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: rs11876941; hg19: chr18-50906031;