Variant 1-230659609-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The ENST00000366669.9(COG2):c.218A>G(p.Asn73Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000379 in 1,613,218 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00063 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

COG2
ENST00000366669.9 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.60

Variant links:

Genes affected

COG2 (HGNC:6546): (component of oligomeric golgi complex 2) This gene encodes a subunit of the conserved oligomeric Golgi complex that is required for maintaining normal structure and activity of the Golgi complex. The encoded protein specifically interacts with the USO1 vesicle docking protein and may be necessary for normal Golgi ribbon formation and trafficking of Golgi enzymes. Mutations of this gene are associated with abnormal glycosylation within the Golgi apparatus. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2009]

COG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027139068).

BP6

Variant 1-230659609-A-G is Benign according to our data. Variant chr1-230659609-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 718942.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00063 (96/152314) while in subpopulation AMR AF= 0.00157 (24/15302). AF 95% confidence interval is 0.00108. There are 1 homozygotes in gnomad4. There are 36 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG2	NM_007357.3 linkuse as main transcript	c.218A>G	p.Asn73Ser	missense_variant	2/18	ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2 linkuse as main transcript	c.218A>G	p.Asn73Ser	missense_variant	2/18		NP_001138508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9 linkuse as main transcript	c.218A>G	p.Asn73Ser	missense_variant	2/18	1	NM_007357.3	ENSP00000355629	P4	Q14746-1

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000652

AC:

163

AN:

250080

Hom.:

AF XY:

0.000548

AC XY:

AN XY:

135064

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00221

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000399

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000388

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.000353

AC:

516

AN:

1460904

Hom.:

Cov.:

AF XY:

0.000318

AC XY:

231

AN XY:

726612

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.000268

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000278

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.000630

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000343

Hom.:

Bravo

AF:

0.000861

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000766

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital disorder of glycosylation, type IIq

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

COG2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 20, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;.;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.027

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Benign

0.23

Sift

Pathogenic

0.0

D;D;T

Sift4G

Benign

0.087

T;T;T

Polyphen

0.45

B;.;.

Vest4

0.50

MVP

0.20

MPC

0.52

ClinPred

0.039

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.67

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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