rs6681346

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007357.3(COG2):c.912T>A(p.Asn304Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,609,674 control chromosomes in the GnomAD database, including 2,181 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 821 hom., cov: 32)

Exomes 𝑓: 0.023 ( 1360 hom. )

Consequence

COG2
NM_007357.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.102

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

congenital disorder of glycosylation, type IIq
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

COG2 links:

ENSG00000305699 (HGNC:):

ENSG00000305699 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011480153).

BP6

Variant 1-230675010-T-A is Benign according to our data. Variant chr1-230675010-T-A is described in ClinVar as Benign. ClinVar VariationId is 478371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG2	NM_007357.3 link	c.912T>A	p.Asn304Lys	missense_variant	Exon 9 of 18	ENST00000366669.9	NP_031383.1	Q14746-1B1ALW7
COG2	NM_001145036.2 link	c.912T>A	p.Asn304Lys	missense_variant	Exon 9 of 18		NP_001138508.1	Q14746-2
COG2	XM_047449445.1 link	c.573T>A	p.Asn191Lys	missense_variant	Exon 7 of 16		XP_047305401.1
LOC107985358	XR_001738517.1 link	n.289A>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9 link	c.912T>A	p.Asn304Lys	missense_variant	Exon 9 of 18	1	NM_007357.3	ENSP00000355629.4		Q14746-1

Frequencies

GnomAD3 genomes

AF:

0.0679

AC:

10334

AN:

152126

Hom.:

821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0395

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.0772

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.00481

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.0516

GnomAD2 exomes

AF:

0.0390

AC:

9687

AN:

248074

AF XY:

0.0390

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.0189

Gnomad ASJ exome

AF:

0.0157

Gnomad EAS exome

AF:

0.0711

Gnomad FIN exome

AF:

0.00528

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.0302

GnomAD4 exome

AF:

0.0230

AC:

33477

AN:

1457430

Hom.:

1360

Cov.:

AF XY:

0.0245

AC XY:

17742

AN XY:

724890

show subpopulations

African (AFR)

AF:

0.203

AC:

6746

AN:

33290

American (AMR)

AF:

0.0207

AC:

913

AN:

44130

Ashkenazi Jewish (ASJ)

AF:

0.0157

AC:

410

AN:

26078

East Asian (EAS)

AF:

0.0679

AC:

2686

AN:

39542

South Asian (SAS)

AF:

0.0932

AC:

7931

AN:

85080

European-Finnish (FIN)

AF:

0.00562

AC:

300

AN:

53354

Middle Eastern (MID)

AF:

0.0465

AC:

268

AN:

5764

European-Non Finnish (NFE)

AF:

0.0109

AC:

12117

AN:

1109964

Other (OTH)

AF:

0.0350

AC:

2106

AN:

60228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1376

2752

4129

5505

6881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

678

1356

2034

2712

3390

<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

AF:

0.0680

AC:

10356

AN:

152244

Hom.:

821

Cov.:

AF XY:

0.0688

AC XY:

5126

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.190

AC:

7899

AN:

41518

American (AMR)

AF:

0.0395

AC:

604

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

AN:

3470

East Asian (EAS)

AF:

0.0778

AC:

403

AN:

5180

South Asian (SAS)

AF:

0.101

AC:

487

AN:

4824

European-Finnish (FIN)

AF:

0.00481

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0106

AC:

721

AN:

68026

Other (OTH)

AF:

0.0553

AC:

117

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

441

882

1322

1763

2204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0216

Hom.:

112

Bravo

AF:

0.0755

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.180

AC:

793

ESP6500EA

AF:

0.0105

AC:

ExAC

AF:

0.0430

AC:

5219

Asia WGS

AF:

0.102

AC:

352

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Congenital disorder of glycosylation, type IIq

Benign:1

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.084

T;.;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.91

D;D;D

MetaRNN

Benign

0.0011

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

L;L;.

PhyloP100

0.10

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.77

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.51

T;T;T

Sift4G

Benign

0.88

T;T;T

Polyphen

0.045

B;.;.

Vest4

0.053

MutPred

0.34

Gain of solvent accessibility (P = 0.0058);Gain of solvent accessibility (P = 0.0058);.;

MPC

0.18

ClinPred

0.0099

GERP RS

-2.2

Varity_R

0.053

gMVP

0.14

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over