rs113173809

Positions:

• chr1-230675112-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.822

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]

LOC107985358 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG2	NM_007357.3	c.1014T>C	p.Asp338Asp	synonymous_variant	9/18	ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2	c.1014T>C	p.Asp338Asp	synonymous_variant	9/18		NP_001138508.1
COG2	XM_047449445.1	c.675T>C	p.Asp225Asp	synonymous_variant	7/16		XP_047305401.1
LOC107985358	XR_001738517.1	n.187A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9	c.1014T>C	p.Asp338Asp	synonymous_variant	9/18	1	NM_007357.3	ENSP00000355629.4

Frequencies

GnomAD3 genomes AF: 0.00409 AC: 623 AN: 152212 Hom.: 3 Cov.: 32

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

GnomAD3 exomes AF: 0.00473 AC: 1178 AN: 248910 Hom.: 5 AF XY: 0.00496 AC XY: 667 AN XY: 134528

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 SAS exome AF: 0.00541

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.: 33 Cov.: 30 AF XY: 0.00587 AC XY: 4260 AN XY: 725812

Gnomad4 AFR exome AF: 0.00138

Gnomad4 AMR exome AF: 0.00300

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00517

Gnomad4 FIN exome AF: 0.00165

Gnomad4 NFE exome AF: 0.00677

Gnomad4 OTH exome AF: 0.00483

GnomAD4 genome AF: 0.00409 AC: 623 AN: 152330 Hom.: 3 Cov.: 32 AF XY: 0.00369 AC XY: 275 AN XY: 74488

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00399

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00683

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00511 Hom.: 1

Bravo AF: 0.00403

Asia WGS AF: 0.00289 AC: 10 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

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	COG2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital disorder of glycosylation, type IIq Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

COG2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 2019

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
DANN	Benign	0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs113173809; hg19: chr1-230810858; COSMIC: COSV64187178;