rs948590

Variant names:

• chr18-52598558-G-A
• rs948590
• NM_005215.4:c.92-153496G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-52598558-G-A
• chr18-52598558-G-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.92-153496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,966 control chromosomes in the GnomAD database, including 11,395 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 0.39 (11395 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCC	NM_005215.4	c.92-153496G>A		intron_variant	Intron 1 of 28	ENST00000442544.7	NP_005206.2
DCC	XM_017025568.2	c.92-153496G>A		intron_variant	Intron 1 of 28		XP_016881057.1
DCC	XM_017025569.2	c.92-153496G>A		intron_variant	Intron 1 of 28		XP_016881058.1
DCC	XM_047437311.1	c.92-153496G>A		intron_variant	Intron 1 of 28		XP_047293267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.92-153496G>A		intron_variant	Intron 1 of 28	1	NM_005215.4	ENSP00000389140.2

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58527 AN: 151848 Hom.: 11390 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.385 AC: 58542 AN: 151966 Hom.: 11395 Cov.: 32 AF XY: 0.380 AC XY: 28222 AN XY: 74270

African (AFR) AF: 0.416 AC: 17218 AN: 41430

American (AMR) AF: 0.359 AC: 5487 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1437 AN: 3472

East Asian (EAS) AF: 0.340 AC: 1749 AN: 5146

South Asian (SAS) AF: 0.359 AC: 1729 AN: 4814

European-Finnish (FIN) AF: 0.303 AC: 3205 AN: 10572

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.387 AC: 26283 AN: 67952

Other (OTH) AF: 0.406 AC: 857 AN: 2110

Alfa AF: 0.379 Hom.: 18923

Bravo AF: 0.391

Asia WGS AF: 0.348 AC: 1215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.039
DANN	Benign	0.74
PhyloP100		-1.7
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: rs948590; hg19: chr18-50124928;