18-52340795-A-G

Position:

chr18-52340795-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_005215.4(DCC):c.8A>G(p.Asn3Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000155 in 1,613,694 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

DCC
NM_005215.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.03

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006219417).

BP6

Variant 18-52340795-A-G is Benign according to our data. Variant chr18-52340795-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3059262.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000177 (27/152158) while in subpopulation EAS AF= 0.00524 (27/5154). AF 95% confidence interval is 0.0037. There are 0 homozygotes in gnomad4. There are 19 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCC	NM_005215.4 linkuse as main transcript	c.8A>G	p.Asn3Ser	missense_variant	1/29	ENST00000442544.7	NP_005206.2	P43146Q49AK4
DCC	XM_017025568.2 linkuse as main transcript	c.8A>G	p.Asn3Ser	missense_variant	1/29		XP_016881057.1
DCC	XM_017025569.2 linkuse as main transcript	c.8A>G	p.Asn3Ser	missense_variant	1/29		XP_016881058.1
DCC	XM_047437311.1 linkuse as main transcript	c.8A>G	p.Asn3Ser	missense_variant	1/29		XP_047293267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7 linkuse as main transcript	c.8A>G	p.Asn3Ser	missense_variant	1/29	1	NM_005215.4	ENSP00000389140.2		P43146

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00503

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000569

AC:

143

AN:

251492

Hom.:

AF XY:

0.000508

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00767

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000153

AC:

223

AN:

1461536

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

117

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00506

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000177

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00524

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000378

Hom.:

Bravo

AF:

0.000332

ExAC

AF:

0.000585

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DCC-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 31, 2020

This variant is classified as likely 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

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

Eigen

Benign

-0.16

Eigen_PC

Benign

0.029

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.59

M_CAP

Benign

0.0092

MetaRNN

Benign

0.0062

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.54

REVEL

Benign

0.055

Sift

Uncertain

0.026

Sift4G

Pathogenic

0.0

Polyphen

0.24

Vest4

0.24

MVP

0.57

MPC

0.14

ClinPred

0.090

GERP RS

4.5

Varity_R

0.12

gMVP

0.38

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