dbSNP rs12046196: COG2:c.1166+399G>A (chr1-230679451-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007357.3(COG2):c.1166+399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 154,946 control chromosomes in the GnomAD database, including 1,643 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1621 hom., cov: 32)

Exomes 𝑓: 0.10 ( 22 hom. )

Consequence

COG2
NM_007357.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.587

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COG2	NM_007357.3 link	c.1166+399G>A	intron_variant	Intron 10 of 17	ENST00000366669.9	NP_031383.1	Q14746-1B1ALW7
COG2	NM_001145036.2 link	c.1166+399G>A	intron_variant	Intron 10 of 17		NP_001138508.1	Q14746-2
COG2	XM_047449445.1 link	c.827+399G>A	intron_variant	Intron 8 of 15		XP_047305401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9 link	c.1166+399G>A		intron_variant	Intron 10 of 17	1	NM_007357.3	ENSP00000355629.4		Q14746-1

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18831

AN:

151978

Hom.:

1620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.0642

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.0681

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0764

Gnomad OTH

AF:

0.103

GnomAD4 exome

AF:

0.101

AC:

287

AN:

2850

Hom.:

Cov.:

AF XY:

0.0986

AC XY:

146

AN XY:

1480

show subpopulations

African (AFR)

AF:

0.178

AC:

AN:

American (AMR)

AF:

0.111

AC:

AN:

208

Ashkenazi Jewish (ASJ)

AF:

0.0270

AC:

AN:

East Asian (EAS)

AF:

0.353

AC:

AN:

102

South Asian (SAS)

AF:

0.160

AC:

AN:

100

European-Finnish (FIN)

AF:

0.114

AC:

AN:

Middle Eastern (MID)

AF:

0.100

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0829

AC:

174

AN:

2100

Other (OTH)

AF:

0.115

AC:

AN:

122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.124

AC:

18845

AN:

152096

Hom.:

1621

Cov.:

AF XY:

0.128

AC XY:

9498

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.172

AC:

7134

AN:

41478

American (AMR)

AF:

0.154

AC:

2351

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0642

AC:

223

AN:

3472

East Asian (EAS)

AF:

0.407

AC:

2103

AN:

5170

South Asian (SAS)

AF:

0.184

AC:

887

AN:

4816

European-Finnish (FIN)

AF:

0.0681

AC:

719

AN:

10562

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0763

AC:

5191

AN:

67994

Other (OTH)

AF:

0.104

AC:

220

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

798

1596

2393

3191

3989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<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:

0.0981

Hom.:

841

Bravo

AF:

0.133

Asia WGS

AF:

0.265

AC:

920

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.14

(source)

DANN

Benign

0.63

PhyloP100

-0.59

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over