18-52752125-G-C

Position:

• chr18-52752125-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005215.4(DCC):​c.163G>C​(p.Gly55Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCC NM_005215.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.628

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCC	NM_005215.4	c.163G>C	p.Gly55Arg	missense_variant	2/29	ENST00000442544.7	NP_005206.2
DCC	XM_017025568.2	c.163G>C	p.Gly55Arg	missense_variant	2/29		XP_016881057.1
DCC	XM_017025569.2	c.163G>C	p.Gly55Arg	missense_variant	2/29		XP_016881058.1
DCC	XM_047437311.1	c.163G>C	p.Gly55Arg	missense_variant	2/29		XP_047293267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.163G>C	p.Gly55Arg	missense_variant	2/29	1	NM_005215.4	ENSP00000389140.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Apr 29, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2021	Not observed at significant frequency in large population cohorts (Lek 2006).; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.067	T;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0090	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.32	N;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.4	N;.
REVEL	Benign	0.20
Sift	Benign	0.22	T;.
Sift4G	Benign	0.39	T;T
Polyphen		0.92	P;.
Vest4		0.29
MutPred		0.77		Loss of loop (P = 0.1242);.;
MVP		0.36
MPC		0.25
ClinPred		0.87	D
GERP RS		5.7
Varity_R		0.20
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-50278495;