18-52906232-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005215.4(DCC):c.601C>G(p.Arg201Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,613,528 control chromosomes in the GnomAD database, including 130,283 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12000 hom., cov: 32)

Exomes 𝑓: 0.39 ( 118283 hom. )

Consequence

DCC
NM_005215.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0770

Publications

61 publications found

Variant links:

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)

DCC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.275568E-5).

BP6

Variant 18-52906232-C-G is Benign according to our data. Variant chr18-52906232-C-G is described in ClinVar as Benign. ClinVar VariationId is 803493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCC	NM_005215.4 link	c.601C>G	p.Arg201Gly	missense_variant	Exon 3 of 29	ENST00000442544.7	NP_005206.2	P43146Q49AK4
DCC	XM_017025568.2 link	c.601C>G	p.Arg201Gly	missense_variant	Exon 3 of 29		XP_016881057.1
DCC	XM_017025569.2 link	c.601C>G	p.Arg201Gly	missense_variant	Exon 3 of 29		XP_016881058.1
DCC	XM_047437311.1 link	c.601C>G	p.Arg201Gly	missense_variant	Exon 3 of 29		XP_047293267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7 link	c.601C>G	p.Arg201Gly	missense_variant	Exon 3 of 29	1	NM_005215.4	ENSP00000389140.2		P43146

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58743

AN:

151792

Hom.:

11990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.498

Gnomad AMR

AF:

0.491

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.546

Gnomad SAS

AF:

0.635

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.393

GnomAD2 exomes

AF:

0.452

AC:

113154

AN:

250512

AF XY:

0.456

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.614

Gnomad ASJ exome

AF:

0.502

Gnomad EAS exome

AF:

0.554

Gnomad FIN exome

AF:

0.387

Gnomad NFE exome

AF:

0.363

Gnomad OTH exome

AF:

0.449

GnomAD4 exome

AF:

0.392

AC:

573444

AN:

1461616

Hom.:

118283

Cov.:

AF XY:

0.399

AC XY:

290411

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.338

AC:

11324

AN:

33476

American (AMR)

AF:

0.598

AC:

26749

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

12885

AN:

26136

East Asian (EAS)

AF:

0.608

AC:

24129

AN:

39672

South Asian (SAS)

AF:

0.623

AC:

53743

AN:

86248

European-Finnish (FIN)

AF:

0.395

AC:

21060

AN:

53368

Middle Eastern (MID)

AF:

0.471

AC:

2714

AN:

5768

European-Non Finnish (NFE)

AF:

0.356

AC:

395839

AN:

1111848

Other (OTH)

AF:

0.414

AC:

25001

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

19415

38831

58246

77662

97077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13014

26028

39042

52056

65070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.387

AC:

58788

AN:

151912

Hom.:

12000

Cov.:

AF XY:

0.396

AC XY:

29386

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.336

AC:

13900

AN:

41406

American (AMR)

AF:

0.492

AC:

7494

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

1703

AN:

3472

East Asian (EAS)

AF:

0.546

AC:

2814

AN:

5150

South Asian (SAS)

AF:

0.634

AC:

3055

AN:

4818

European-Finnish (FIN)

AF:

0.399

AC:

4207

AN:

10552

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24196

AN:

67968

Other (OTH)

AF:

0.398

AC:

839

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1805

3609

5414

7218

9023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.332

Hom.:

2751

Bravo

AF:

0.392

TwinsUK

AF:

0.358

AC:

1326

ALSPAC

AF:

0.387

AC:

1490

ESP6500AA

AF:

0.344

AC:

1517

ESP6500EA

AF:

0.367

AC:

3157

ExAC

AF:

0.444

AC:

53851

EpiCase

AF:

0.383

EpiControl

AF:

0.389

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 11, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 9440618) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mirror movements 1

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Gaze palsy, familial horizontal, with progressive scoliosis, 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.18

T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

0.000033

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.41

N;.

PhyloP100

0.077

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.3

N;.

REVEL

Benign

0.11

Sift

Benign

0.11

T;.

Sift4G

Benign

0.076

T;T

Polyphen

0.80

P;.

Vest4

0.67

MPC

0.26

ClinPred

0.035

GERP RS

-0.49

Varity_R

0.11

gMVP

0.67

Mutation Taster

=68/32

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over