Variant chr7-130652931-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_012133.6(COPG2):c.261G>A(p.Met87Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000437 in 1,601,904 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

COPG2
NM_012133.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.93

Variant links:

Genes affected

COPG2 (HGNC:2237): (COPI coat complex subunit gamma 2) Predicted to enable structural molecule activity. Involved in intra-Golgi vesicle-mediated transport. Part of COPI vesicle coat. [provided by Alliance of Genome Resources, Apr 2022]

COPG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COPG2	NM_012133.6 linkuse as main transcript	c.261G>A	p.Met87Ile	missense_variant	5/24	ENST00000425248.5	NP_036265.3	Q9UBF2-1A0A140VK12
COPG2	NM_001290033.2 linkuse as main transcript	c.261G>A	p.Met87Ile	missense_variant	5/20		NP_001276962.1	Q9UBF2-2Q9NSM7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COPG2	ENST00000425248.5 linkuse as main transcript	c.261G>A	p.Met87Ile	missense_variant	5/24	1	NM_012133.6	ENSP00000402346.2		Q9UBF2-1
COPG2	ENST00000330992.8 linkuse as main transcript	c.261G>A	p.Met87Ile	missense_variant	5/20	1		ENSP00000331218.8		Q9UBF2-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000126

AC:

AN:

238176

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

128718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000572

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000342

GnomAD4 exome

AF:

0.00000414

AC:

AN:

1449754

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

720680

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.06e-7

Gnomad4 OTH exome

AF:

0.0000667

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000578

AC:

AN:

3474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.261G>A (p.M87I) alteration is located in exon 1 (coding exon 1) of the COPG2 gene. This alteration results from a G to A substitution at nucleotide position 261, causing the methionine (M) at amino acid position 87 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.020

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Benign

-0.85

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.1

.;D

REVEL

Uncertain

0.38

Sift

Benign

0.038

.;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.97

D;.

Vest4

0.77

MutPred

0.71

Loss of catalytic residue at M87 (P = 0.0134);Loss of catalytic residue at M87 (P = 0.0134);

MVP

0.87

ClinPred

0.95

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.54

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over