1-230693393-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007357.3(COG2):c.2217A>G(p.Ter739Ter) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,595,614 control chromosomes in the GnomAD database, including 50,880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5349 hom., cov: 33)

Exomes 𝑓: 0.23 ( 45531 hom. )

Consequence

COG2
NM_007357.3 stop_retained

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.761

Publications

21 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 links:

AGT (HGNC:333): (angiotensinogen) The protein encoded by this gene, pre-angiotensinogen or angiotensinogen precursor, is expressed in the liver and is cleaved by the enzyme renin in response to lowered blood pressure. The resulting product, angiotensin I, is then cleaved by angiotensin converting enzyme (ACE) to generate the physiologically active enzyme angiotensin II. The protein is involved in maintaining blood pressure, body fluid and electrolyte homeostasis, and in the pathogenesis of essential hypertension and preeclampsia. Mutations in this gene are associated with susceptibility to essential hypertension, and can cause renal tubular dysgenesis, a severe disorder of renal tubular development. Defects in this gene have also been associated with non-familial structural atrial fibrillation, and inflammatory bowel disease. [provided by RefSeq, Nov 2019]

AGT Gene-Disease associations (from GenCC):

renal tubular dysgenesis of genetic origin
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

AGT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-230693393-A-G is Benign according to our data. Variant chr1-230693393-A-G is described in ClinVar as Benign. ClinVar VariationId is 1164695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.761 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007357.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG2	NM_007357.3	MANE Select	c.2217A>G	p.Ter739Ter	stop_retained	Exon 18 of 18	NP_031383.1
	COG2	NM_001145036.2		c.2214A>G	p.Ter738Ter	stop_retained	Exon 18 of 18	NP_001138508.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COG2	ENST00000366669.9	TSL:1 MANE Select	c.2217A>G	p.Ter739Ter	stop_retained	Exon 18 of 18	ENSP00000355629.4
COG2	ENST00000366668.7	TSL:1	c.2214A>G	p.Ter738Ter	stop_retained	Exon 18 of 18	ENSP00000355628.3
COG2	ENST00000534989.1	TSL:2	c.2040A>G	p.Ter680Ter	stop_retained	Exon 18 of 18	ENSP00000440349.1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37938

AN:

152054

Hom.:

5342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.583

Gnomad SAS

AF:

0.312

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.238

GnomAD2 exomes

AF:

0.302

AC:

74383

AN:

246524

AF XY:

0.290

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.538

Gnomad ASJ exome

AF:

0.182

Gnomad EAS exome

AF:

0.595

Gnomad FIN exome

AF:

0.284

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.235

AC:

339184

AN:

1443442

Hom.:

45531

Cov.:

AF XY:

0.236

AC XY:

169270

AN XY:

718438

show subpopulations

African (AFR)

AF:

0.217

AC:

7132

AN:

32938

American (AMR)

AF:

0.521

AC:

22876

AN:

43942

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4605

AN:

25870

East Asian (EAS)

AF:

0.556

AC:

21939

AN:

39474

South Asian (SAS)

AF:

0.288

AC:

24413

AN:

84658

European-Finnish (FIN)

AF:

0.276

AC:

14739

AN:

53328

Middle Eastern (MID)

AF:

0.178

AC:

1016

AN:

5718

European-Non Finnish (NFE)

AF:

0.208

AC:

227858

AN:

1097804

Other (OTH)

AF:

0.245

AC:

14606

AN:

59710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

10598

21195

31793

42390

52988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8080

16160

24240

32320

40400

<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:

0.250

AC:

37977

AN:

152172

Hom.:

5349

Cov.:

AF XY:

0.257

AC XY:

19137

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.210

AC:

8734

AN:

41524

American (AMR)

AF:

0.371

AC:

5676

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

644

AN:

3466

East Asian (EAS)

AF:

0.582

AC:

2999

AN:

5154

South Asian (SAS)

AF:

0.312

AC:

1505

AN:

4828

European-Finnish (FIN)

AF:

0.288

AC:

3048

AN:

10594

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.213

AC:

14495

AN:

67998

Other (OTH)

AF:

0.245

AC:

517

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1431

2861

4292

5722

7153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.235

Hom.:

5636

Bravo

AF:

0.260

Asia WGS

AF:

0.443

AC:

1539

AN:

3478

EpiCase

AF:

0.205

EpiControl

AF:

0.203

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Sep 04, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Congenital disorder of glycosylation, type IIq

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.9

(source)

DANN

Benign

0.57

PhyloP100

0.76

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over