1-230659574-C-T

Variant names:

• chr1-230659574-C-T
• rs79749108
• NM_007357.3:c.183C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_007357.3(COG2):​c.183C>T​(p.Val61Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000731 in 1,613,948 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00041 (7 hom.)
• Consequence: COG2 NM_007357.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43
• Publications: 0 publications found

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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000305699 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 1-230659574-C-T is Benign according to our data. Variant chr1-230659574-C-T is described in ClinVar as Benign. ClinVar VariationId is 709599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.43 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00377 (574/152260) while in subpopulation AFR AF = 0.013 (542/41536). AF 95% confidence interval is 0.0121. There are 4 homozygotes in GnomAd4. There are 270 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007357.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG2	NM_007357.3	MANE Select	c.183C>T	p.Val61Val	synonymous	Exon 2 of 18	NP_031383.1	Q14746-1
	COG2	NM_001145036.2		c.183C>T	p.Val61Val	synonymous	Exon 2 of 18	NP_001138508.1	Q14746-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG2	ENST00000366669.9	TSL:1 MANE Select	c.183C>T	p.Val61Val	synonymous	Exon 2 of 18	ENSP00000355629.4	Q14746-1
	COG2	ENST00000366668.7	TSL:1	c.183C>T	p.Val61Val	synonymous	Exon 2 of 18	ENSP00000355628.3	Q14746-2
	COG2	ENST00000921491.1		c.183C>T	p.Val61Val	synonymous	Exon 2 of 18	ENSP00000591550.1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 571 AN: 152142 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000935 AC: 235 AN: 251208 AF XY: 0.000582

Gnomad AFR exome AF: 0.0134

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000415 AC: 606 AN: 1461688 Hom.: 7 Cov.: 31 AF XY: 0.000320 AC XY: 233 AN XY: 727146

African (AFR) AF: 0.0147 AC: 492 AN: 33470

American (AMR) AF: 0.000626 AC: 28 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111930

Other (OTH) AF: 0.000911 AC: 55 AN: 60388

GnomAD4 genome AF: 0.00377 AC: 574 AN: 152260 Hom.: 4 Cov.: 33 AF XY: 0.00363 AC XY: 270 AN XY: 74468

African (AFR) AF: 0.0130 AC: 542 AN: 41536

American (AMR) AF: 0.00150 AC: 23 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00144 Hom.: 3

Bravo AF: 0.00419

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital disorder of glycosylation, type IIq (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs79749108; hg19: chr1-230795320;