rs113173809

Variant names:

• chr1-230675112-T-C
• rs113173809
• NM_007357.3:c.1014T>C

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.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
• Publications: 2 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: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen

ENSG00000305699 (HGNC:):

ACMG classification

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

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.1014T>C	p.Asp338Asp	synonymous	Exon 9 of 18	NP_031383.1	Q14746-1
	COG2	NM_001145036.2		c.1014T>C	p.Asp338Asp	synonymous	Exon 9 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.1014T>C	p.Asp338Asp	synonymous	Exon 9 of 18	ENSP00000355629.4	Q14746-1
	COG2	ENST00000366668.7	TSL:1	c.1014T>C	p.Asp338Asp	synonymous	Exon 9 of 18	ENSP00000355628.3	Q14746-2
	COG2	ENST00000921491.1		c.1014T>C	p.Asp338Asp	synonymous	Exon 9 of 18	ENSP00000591550.1

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

GnomAD2 exomes AF: 0.00473 AC: 1178 AN: 248910 AF XY: 0.00496

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

African (AFR) AF: 0.00138 AC: 46 AN: 33414

American (AMR) AF: 0.00300 AC: 133 AN: 44370

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26098

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39644

South Asian (SAS) AF: 0.00517 AC: 442 AN: 85498

European-Finnish (FIN) AF: 0.00165 AC: 88 AN: 53364

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5762

European-Non Finnish (NFE) AF: 0.00677 AC: 7515 AN: 1110862

Other (OTH) AF: 0.00483 AC: 291 AN: 60300

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

African (AFR) AF: 0.00149 AC: 62 AN: 41576

American (AMR) AF: 0.00399 AC: 61 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4826

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00683 AC: 465 AN: 68036

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

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

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	COG2-related disorder (1)
-	-	1	Congenital disorder of glycosylation, type IIq (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.1
DANN	Benign	0.25
PhyloP100		0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs113173809; hg19: chr1-230810858; COSMIC: COSV64187178;