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GeneBe

18-52752265-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_005215.4(DCC):c.303C>T(p.Asn101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,614,144 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00059 ( 8 hom. )

Consequence

DCC
NM_005215.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0920
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 18-52752265-C-T is Benign according to our data. Variant chr18-52752265-C-T is described in ClinVar as [Benign]. Clinvar id is 780478.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.092 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00653 (995/152272) while in subpopulation AFR AF= 0.0229 (951/41560). AF 95% confidence interval is 0.0217. There are 11 homozygotes in gnomad4. There are 497 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 11 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DCCNM_005215.4 linkuse as main transcriptc.303C>T p.Asn101= synonymous_variant 2/29 ENST00000442544.7
DCCXM_017025568.2 linkuse as main transcriptc.303C>T p.Asn101= synonymous_variant 2/29
DCCXM_017025569.2 linkuse as main transcriptc.303C>T p.Asn101= synonymous_variant 2/29
DCCXM_047437311.1 linkuse as main transcriptc.303C>T p.Asn101= synonymous_variant 2/29

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DCCENST00000442544.7 linkuse as main transcriptc.303C>T p.Asn101= synonymous_variant 2/291 NM_005215.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00653
AC:
993
AN:
152154
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0229
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00167
AC:
420
AN:
251488
Hom.:
4
AF XY:
0.00113
AC XY:
154
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.0235
Gnomad AMR exome
AF:
0.000925
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:
0.0000352
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000594
AC:
869
AN:
1461872
Hom.:
8
Cov.:
31
AF XY:
0.000470
AC XY:
342
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0215
Gnomad4 AMR exome
AF:
0.00101
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.00139
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00653
AC:
995
AN:
152272
Hom.:
11
Cov.:
32
AF XY:
0.00668
AC XY:
497
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0229
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00371
Hom.:
4
Bravo
AF:
0.00732
Asia WGS
AF:
0.00115
AC:
6
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
8.4
Dann
Benign
0.61

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

LitVar

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

Other links and lift over

dbSNP: rs73457796; hg19: chr18-50278635; API