Variant 1-230660629-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007357.3(COG2):c.235-129A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 516,244 control chromosomes in the GnomAD database, including 16,605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5041 hom., cov: 33)

Exomes 𝑓: 0.24 ( 11564 hom. )

Consequence

COG2
NM_007357.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.325

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-230660629-A-C is Benign according to our data. Variant chr1-230660629-A-C is described in ClinVar as [Benign]. Clinvar id is 1242323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG2	NM_007357.3 linkuse as main transcript	c.235-129A>C		intron_variant		ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2 linkuse as main transcript	c.235-129A>C		intron_variant			NP_001138508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9 linkuse as main transcript	c.235-129A>C		intron_variant		1	NM_007357.3	ENSP00000355629	P4	Q14746-1

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37899

AN:

152002

Hom.:

5034

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.246

GnomAD4 exome

AF:

0.240

AC:

87356

AN:

364124

Hom.:

11564

AF XY:

0.245

AC XY:

46725

AN XY:

190770

show subpopulations

Gnomad4 AFR exome

AF:

0.303

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.416

Gnomad4 SAS exome

AF:

0.434

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.240

GnomAD4 genome

AF:

0.249

AC:

37927

AN:

152120

Hom.:

5041

Cov.:

AF XY:

0.252

AC XY:

18742

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.303

Gnomad4 AMR

AF:

0.240

Gnomad4 ASJ

AF:

0.216

Gnomad4 EAS

AF:

0.435

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.215

Gnomad4 OTH

AF:

0.247

Alfa

AF:

0.231

Hom.:

2001

Bravo

AF:

0.254

Asia WGS

AF:

0.370

AC:

1287

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.76

DANN

Benign

0.80

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