NM_007357.3:c.1014T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_007357.3(COG2):c.1014T>C(p.Asp338Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,611,642 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 33 hom. )

Consequence

COG2
NM_007357.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.822

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:

ENSG00000305699 (HGNC:):

ENSG00000305699 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=-0.6).

BP6

Variant 1-230675112-T-C is Benign according to our data. Variant chr1-230675112-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 478370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.822 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00409 (623/152330) while in subpopulation NFE AF = 0.00683 (465/68036). AF 95% confidence interval is 0.00632. There are 3 homozygotes in GnomAd4. There are 275 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG2	NM_007357.3 link	c.1014T>C	p.Asp338Asp	synonymous_variant	Exon 9 of 18	ENST00000366669.9	NP_031383.1	Q14746-1B1ALW7
COG2	NM_001145036.2 link	c.1014T>C	p.Asp338Asp	synonymous_variant	Exon 9 of 18		NP_001138508.1	Q14746-2
COG2	XM_047449445.1 link	c.675T>C	p.Asp225Asp	synonymous_variant	Exon 7 of 16		XP_047305401.1
LOC107985358	XR_001738517.1 link	n.187A>G		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.1014T>C	p.Asp338Asp	synonymous_variant	Exon 9 of 18	1	NM_007357.3	ENSP00000355629.4		Q14746-1

Frequencies

GnomAD3 genomes

AF:

0.00409

AC:

623

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00683

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00473

AC:

1178

AN:

248910

AF XY:

0.00496

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00262

Gnomad ASJ exome

AF:

0.000896

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.00740

Gnomad OTH exome

AF:

0.00547

GnomAD4 exome

AF:

0.00588

AC:

8575

AN:

1459312

Hom.:

Cov.:

AF XY:

0.00587

AC XY:

4260

AN XY:

725812

show subpopulations

African (AFR)

AF:

0.00138

AC:

AN:

33414

American (AMR)

AF:

0.00300

AC:

133

AN:

44370

Ashkenazi Jewish (ASJ)

AF:

0.00103

AC:

AN:

26098

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39644

South Asian (SAS)

AF:

0.00517

AC:

442

AN:

85498

European-Finnish (FIN)

AF:

0.00165

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00555

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00677

AC:

7515

AN:

1110862

Other (OTH)

AF:

0.00483

AC:

291

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

396

793

1189

1586

1982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

294

588

882

1176

1470

<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:

0.00409

AC:

623

AN:

152330

Hom.:

Cov.:

AF XY:

0.00369

AC XY:

275

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

41576

American (AMR)

AF:

0.00399

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00311

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00683

AC:

465

AN:

68036

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00511

Hom.:

Bravo

AF:

0.00403

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00670

EpiControl

AF:

0.00690

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

COG2: BP4, BP7, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Congenital disorder of glycosylation, type IIq

Benign:1

Nov 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

COG2-related disorder

Benign:1

Jul 12, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.1

(source)

DANN

Benign

0.25

PhyloP100

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism

(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