rs6681346

Positions:

• chr1-230675010-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007357.3(COG2):​c.912T>A​(p.Asn304Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,609,674 control chromosomes in the GnomAD database, including 2,181 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (821 hom., cov: 32)
  • Exomes 𝑓: 0.023 (1360 hom.)
• Consequence: COG2 NM_007357.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.102

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011480153).
• BP6: Variant 1-230675010-T-A is Benign according to our data. Variant chr1-230675010-T-A is described in ClinVar as [Benign]. Clinvar id is 478371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG2	NM_007357.3	c.912T>A	p.Asn304Lys	missense_variant	9/18	ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2	c.912T>A	p.Asn304Lys	missense_variant	9/18		NP_001138508.1
COG2	XM_047449445.1	c.573T>A	p.Asn191Lys	missense_variant	7/16		XP_047305401.1
LOC107985358	XR_001738517.1	n.289A>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9	c.912T>A	p.Asn304Lys	missense_variant	9/18	1	NM_007357.3	ENSP00000355629.4

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10334 AN: 152126 Hom.: 821 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.0772

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.00481

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0516

GnomAD3 exomes AF: 0.0390 AC: 9687 AN: 248074 Hom.: 592 AF XY: 0.0390 AC XY: 5228 AN XY: 134100

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.0189

Gnomad ASJ exome AF: 0.0157

Gnomad EAS exome AF: 0.0711

Gnomad SAS exome AF: 0.0969

Gnomad FIN exome AF: 0.00528

Gnomad NFE exome AF: 0.0107

Gnomad OTH exome AF: 0.0302

GnomAD4 exome AF: 0.0230 AC: 33477 AN: 1457430 Hom.: 1360 Cov.: 30 AF XY: 0.0245 AC XY: 17742 AN XY: 724890

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.0207

Gnomad4 ASJ exome AF: 0.0157

Gnomad4 EAS exome AF: 0.0679

Gnomad4 SAS exome AF: 0.0932

Gnomad4 FIN exome AF: 0.00562

Gnomad4 NFE exome AF: 0.0109

Gnomad4 OTH exome AF: 0.0350

GnomAD4 genome AF: 0.0680 AC: 10356 AN: 152244 Hom.: 821 Cov.: 32 AF XY: 0.0688 AC XY: 5126 AN XY: 74452

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.0395

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.0778

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.00481

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0216 Hom.: 112

Bravo AF: 0.0755

TwinsUK AF: 0.0121 AC: 45

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.180 AC: 793

ESP6500EA AF: 0.0105 AC: 90

ExAC AF: 0.0430 AC: 5219

Asia WGS AF: 0.102 AC: 352 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 10, 2019	- -

Congenital disorder of glycosylation, type IIq Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.084	T;.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.91	D;D;D
MetaRNN	Benign	0.0011	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.77	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.88	T;T;T
Polyphen		0.045	B;.;.
Vest4		0.053
MutPred		0.34		Gain of solvent accessibility (P = 0.0058);Gain of solvent accessibility (P = 0.0058);.;
MPC		0.18
ClinPred		0.0099	T
GERP RS		-2.2
Varity_R		0.053
gMVP		0.14

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: rs6681346; hg19: chr1-230810756;