GeneBe

rs754914260

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_005215.4(DCC):​c.823C>A​(p.Arg275Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DCC
NM_005215.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92

Publications

6 publications found
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 Gene-Disease associations (from GenCC):
  • mirror movements 1
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
  • mirror movements 1 and/or agenesis of the corpus callosum
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • gaze palsy, familial horizontal, with progressive scoliosis, 2
    Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics
  • connective tissue disorder
    Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
  • familial congenital mirror movements
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Kallmann syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • colorectal cancer
    Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)
  • esophageal cancer
    Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.22).
BP7
Synonymous conserved (PhyloP=1.92 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCCNM_005215.4 linkc.823C>A p.Arg275Arg synonymous_variant Exon 4 of 29 ENST00000442544.7 NP_005206.2 P43146Q49AK4
DCCXM_017025568.2 linkc.823C>A p.Arg275Arg synonymous_variant Exon 4 of 29 XP_016881057.1
DCCXM_017025569.2 linkc.823C>A p.Arg275Arg synonymous_variant Exon 4 of 29 XP_016881058.1
DCCXM_047437311.1 linkc.823C>A p.Arg275Arg synonymous_variant Exon 4 of 29 XP_047293267.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DCCENST00000442544.7 linkc.823C>A p.Arg275Arg synonymous_variant Exon 4 of 29 1 NM_005215.4 ENSP00000389140.2 P43146
DCCENST00000304775.12 linkn.622C>A non_coding_transcript_exon_variant Exon 3 of 19 1 ENSP00000304146.8 H0Y2Q5
DCCENST00000579883.1 linkn.34C>A non_coding_transcript_exon_variant Exon 1 of 3 4
DCCENST00000584710.5 linkn.49C>A non_coding_transcript_exon_variant Exon 1 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000399
AC:
1
AN:
250852
AF XY:
0.00000738
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461034
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726822
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33444
American (AMR)
AF:
0.00
AC:
0
AN:
44646
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26108
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39670
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86246
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53386
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111424
Other (OTH)
AF:
0.00
AC:
0
AN:
60344
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.22
CADD
Benign
13
DANN
Benign
0.69
PhyloP100
1.9

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

Other links and lift over

dbSNP: rs754914260; hg19: chr18-50450202; COSMIC: COSV59130602; API