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GeneBe

1-230691559-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_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. 13/21 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

3
16

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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COG2NM_007357.3 linkuse as main transcriptc.2110G>A p.Glu704Lys missense_variant 17/18 ENST00000366669.9
COG2NM_001145036.2 linkuse as main transcriptc.2107G>A p.Glu703Lys missense_variant 17/18
COG2XM_047449445.1 linkuse as main transcriptc.1771G>A p.Glu591Lys missense_variant 15/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COG2ENST00000366669.9 linkuse as main transcriptc.2110G>A p.Glu704Lys missense_variant 17/181 NM_007357.3 P4Q14746-1

Frequencies

GnomAD3 genomes
AF:
0.000177
AC:
27
AN:
152216
Hom.:
0
Cov.:
32
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
GnomAD3 exomes
AF:
0.000243
AC:
60
AN:
246974
Hom.:
0
AF XY:
0.000210
AC XY:
28
AN XY:
133614
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 SAS 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.:
0
Cov.:
30
AF XY:
0.000237
AC XY:
172
AN XY:
725100
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000681
Gnomad4 ASJ exome
AF:
0.00292
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000218
Gnomad4 OTH exome
AF:
0.000316
GnomAD4 genome
AF:
0.000177
AC:
27
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000353
Hom.:
0
Bravo
AF:
0.000196
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000148
AC:
18
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
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 24, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.37
Cadd
Benign
20
Dann
Uncertain
1.0
DEOGEN2
Benign
0.098
T;.;T
Eigen
Benign
0.051
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.057
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Benign
0.46
T
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
T
GERP RS
5.6
Varity_R
0.29
gMVP
0.37

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.

Other links and lift over

dbSNP: rs140155560; hg19: chr1-230827305; COSMIC: COSV64186706; COSMIC: COSV64186706; API