chr18-53526629-C-A

Position:

• chr18-53526629-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The ENST00000442544.7(DCC):​c.4124C>A​(p.Pro1375His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCC ENST00000442544.7 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.70

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]

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

LOC124904304 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 18-53526629-C-A is Pathogenic according to our data. Variant chr18-53526629-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 17074.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.3034373). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCC	NM_005215.4	c.4124C>A	p.Pro1375His	missense_variant	28/29	ENST00000442544.7	NP_005206.2
LOC124904304	XR_007066375.1	n.67-21309G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCC	ENST00000442544.7	c.4124C>A	p.Pro1375His	missense_variant	28/29	1	NM_005215.4	ENSP00000389140	P1
LINC01917	ENST00000650275.1	n.360+6721G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Carcinoma of colon Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 1994

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Benign	0.93
DEOGEN2	Benign	0.044	T;.;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.85	L;.;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.10	N;.;.
REVEL	Benign	0.093
Sift	Benign	0.58	T;.;.
Sift4G	Benign	0.67	T;T;T
Polyphen		0.60	P;.;.
Vest4		0.50
MutPred		0.48		Loss of glycosylation at P1375 (P = 0.0148);.;.;
MVP		0.42
MPC		0.63
ClinPred		0.77	D
GERP RS		5.5
Varity_R		0.17
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

Other links and lift over

dbSNP: rs387906555; hg19: chr18-51052999; COSMIC: COSV101473444; COSMIC: COSV101473444;