NM_004766.3:c.760C>T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PP3_ModeratePP5
The NM_004766.3(COPB2):c.760C>T(p.Arg254Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
COPB2
NM_004766.3 missense
NM_004766.3 missense
Scores
10
6
3
Clinical Significance
Conservation
PhyloP100: 5.55
Publications
7 publications found
Genes affected
COPB2 (HGNC:2232): (COPI coat complex subunit beta 2) The Golgi coatomer complex (see MIM 601924) constitutes the coat of nonclathrin-coated vesicles and is essential for Golgi budding and vesicular trafficking. It consists of 7 protein subunits, including COPB2.[supplied by OMIM, Jul 2002]
COPB2 Gene-Disease associations (from GenCC):
- osteoporosis, childhood- or juvenile-onset, with developmental delayInheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- autosomal recessive primary microcephalyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- microcephaly 19, primary, autosomal recessiveInheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.891
PP5
Variant 3-139373800-G-A is Pathogenic according to our data. Variant chr3-139373800-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 446713.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COPB2 | NM_004766.3 | c.760C>T | p.Arg254Cys | missense_variant | Exon 8 of 22 | ENST00000333188.10 | NP_004757.1 | |
COPB2 | NM_001410834.1 | c.673C>T | p.Arg225Cys | missense_variant | Exon 9 of 23 | NP_001397763.1 | ||
COPB2 | NR_023350.1 | n.969C>T | non_coding_transcript_exon_variant | Exon 8 of 22 | ||||
COPB2 | XM_047449233.1 | c.133-388C>T | intron_variant | Intron 2 of 15 | XP_047305189.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151986Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
6
AN:
151986
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000797 AC: 2AN: 250914 AF XY: 0.00000737 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
250914
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461700Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727154 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
1461700
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
727154
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44710
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26120
East Asian (EAS)
AF:
AC:
0
AN:
39688
South Asian (SAS)
AF:
AC:
0
AN:
86234
European-Finnish (FIN)
AF:
AC:
0
AN:
53392
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1111926
Other (OTH)
AF:
AC:
0
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1
2
2
3
4
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
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>80
Age
GnomAD4 genome AF: 0.0000395 AC: 6AN: 151986Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74214 show subpopulations
GnomAD4 genome
AF:
AC:
6
AN:
151986
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74214
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41366
American (AMR)
AF:
AC:
1
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5178
South Asian (SAS)
AF:
AC:
0
AN:
4806
European-Finnish (FIN)
AF:
AC:
0
AN:
10562
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
4
AN:
68016
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.533
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Microcephaly 19, primary, autosomal recessive Pathogenic:1
May 24, 2022
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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