Variant chr18-53499457-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The ENST00000442544.7(DCC):c.4058C>T(p.Pro1353Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

DCC
ENST00000442544.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

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:

LINC01917 (HGNC:52736): (long intergenic non-protein coding RNA 1917)

LINC01917 links:

LOC124904304 (HGNC:):

LOC124904304 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCC	NM_005215.4 linkuse as main transcript	c.4058C>T	p.Pro1353Leu	missense_variant	27/29	ENST00000442544.7	NP_005206.2
LOC124904304	XR_007066375.1 linkuse as main transcript	n.164+5766G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7 linkuse as main transcript	c.4058C>T	p.Pro1353Leu	missense_variant	27/29	1	NM_005215.4	ENSP00000389140	P1
LINC01917	ENST00000650275.1 linkuse as main transcript	n.458+5766G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251476

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Aug 23, 2019

Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

T;.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.0059

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-4.4

D;.;.

REVEL

Benign

0.28

Sift

Benign

0.053

T;.;.

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.80

P;.;.

Vest4

0.54

MutPred

0.56

Loss of glycosylation at P1353 (P = 0.0202);.;.;

MVP

0.55

MPC

0.42

ClinPred

0.80

GERP RS

6.2

Varity_R

0.13

gMVP

0.36

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