Variant 18-52752316-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005215.4(DCC):c.354G>A(p.Glu118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,613,824 control chromosomes in the GnomAD database, including 13,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.099 ( 951 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13007 hom. )

Consequence

DCC
NM_005215.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.122

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 18-52752316-G-A is Benign according to our data. Variant chr18-52752316-G-A is described in ClinVar as [Benign]. Clinvar id is 1255455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.122 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DCC	NM_005215.4 linkuse as main transcript	c.354G>A	p.Glu118=	synonymous_variant	2/29	ENST00000442544.7
DCC	XM_017025568.2 linkuse as main transcript	c.354G>A	p.Glu118=	synonymous_variant	2/29
DCC	XM_017025569.2 linkuse as main transcript	c.354G>A	p.Glu118=	synonymous_variant	2/29
DCC	XM_047437311.1 linkuse as main transcript	c.354G>A	p.Glu118=	synonymous_variant	2/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCC	ENST00000442544.7 linkuse as main transcript	c.354G>A	p.Glu118=	synonymous_variant	2/29	1	NM_005215.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0992

AC:

15084

AN:

152054

Hom.:

952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0411

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.0995

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0720

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.139

GnomAD3 exomes

AF:

0.107

AC:

26961

AN:

251114

Hom.:

1813

AF XY:

0.113

AC XY:

15342

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.0367

Gnomad AMR exome

AF:

0.0687

Gnomad ASJ exome

AF:

0.220

Gnomad EAS exome

AF:

0.000815

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0779

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.128

AC:

186592

AN:

1461652

Hom.:

13007

Cov.:

AF XY:

0.128

AC XY:

93281

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.0379

Gnomad4 AMR exome

AF:

0.0744

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.0787

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.0991

AC:

15077

AN:

152172

Hom.:

951

Cov.:

AF XY:

0.0951

AC XY:

7078

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0410

Gnomad4 AMR

AF:

0.0993

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.0720

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.131

Hom.:

743

Bravo

AF:

0.0979

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

EpiCase

AF:

0.148

EpiControl

AF:

0.157

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Gaze palsy, familial horizontal, with progressive scoliosis, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Mirror movements 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

DCC-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.0

DANN

Benign

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over