1-230691559-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_007357.3(COG2):c.2110G>A(p.Glu704Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000228 in 1,610,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

COG2
NM_007357.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.52

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057067335).

BP6

Variant 1-230691559-G-A is Benign according to our data. Variant chr1-230691559-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 752608.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000177 (27/152216) while in subpopulation NFE AF = 0.000309 (21/68040). AF 95% confidence interval is 0.000207. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG2	NM_007357.3 link	c.2110G>A	p.Glu704Lys	missense_variant	Exon 17 of 18	ENST00000366669.9	NP_031383.1	Q14746-1B1ALW7
COG2	NM_001145036.2 link	c.2107G>A	p.Glu703Lys	missense_variant	Exon 17 of 18		NP_001138508.1	Q14746-2
COG2	XM_047449445.1 link	c.1771G>A	p.Glu591Lys	missense_variant	Exon 15 of 16		XP_047305401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9 link	c.2110G>A	p.Glu704Lys	missense_variant	Exon 17 of 18	1	NM_007357.3	ENSP00000355629.4		Q14746-1

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000243

AC:

AN:

246974

AF XY:

0.000210

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000592

Gnomad ASJ exome

AF:

0.00252

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000215

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000233

AC:

340

AN:

1458008

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

172

AN XY:

725100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

33296

Gnomad4 AMR exome

AF:

0.0000681

AC:

AN:

44030

Gnomad4 ASJ exome

AF:

0.00292

AC:

AN:

26010

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39602

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

85536

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53360

Gnomad4 NFE exome

AF:

0.000218

AC:

242

AN:

1110500

Gnomad4 Remaining exome

AF:

0.000316

AC:

AN:

60204

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

100

<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:

0.000177

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000482

AC:

0.0000482486

AN:

0.0000482486

Gnomad4 AMR

AF:

0.0000654

AC:

0.0000654108

AN:

0.0000654108

Gnomad4 ASJ

AF:

0.000576

AC:

0.000576369

AN:

0.000576369

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000309

AC:

0.000308642

AN:

0.000308642

Gnomad4 OTH

AF:

0.000478

AC:

0.000478011

AN:

0.000478011

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.000338

Hom.:

Bravo

AF:

0.000196

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.000711

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital disorder of glycosylation, type IIq

Benign:1

Jan 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

T;.;T

Eigen

Benign

0.051

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.057

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.89

N;N;N

REVEL

Benign

0.091

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.015

B;.;.

Vest4

0.51

MVP

0.20

MPC

0.17

ClinPred

0.052

GERP RS

5.6

Varity_R

0.29

gMVP

0.37

Mutation Taster

=69/31

polymorphism

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

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