1-230642745-G-C

Variant names:

• chr1-230642745-G-C
• rs4846864
• NM_007357.3:c.72+67G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007357.3(COG2):​c.72+67G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,487,484 control chromosomes in the GnomAD database, including 357,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40983 hom., cov: 34)
  • Exomes 𝑓: 0.69 (316726 hom.)
• Consequence: COG2 NM_007357.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.595
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-230642745-G-C is Benign according to our data. Variant chr1-230642745-G-C is described in ClinVar as Benign. ClinVar VariationId is 1245452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

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.72+67G>C		intron	N/A	NP_031383.1	Q14746-1
	COG2	NM_001145036.2		c.72+67G>C		intron	N/A	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.72+67G>C		intron	N/A	ENSP00000355629.4	Q14746-1
	COG2	ENST00000366668.7	TSL:1	c.72+67G>C		intron	N/A	ENSP00000355628.3	Q14746-2
	COG2	ENST00000921491.1		c.72+67G>C		intron	N/A	ENSP00000591550.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110801 AN: 152124 Hom.: 40924 Cov.: 34

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.724

GnomAD4 exome AF: 0.686 AC: 915379 AN: 1335242 Hom.: 316726 Cov.: 19 AF XY: 0.688 AC XY: 456160 AN XY: 662584

African (AFR) AF: 0.812 AC: 23848 AN: 29354

American (AMR) AF: 0.840 AC: 29003 AN: 34516

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 16430 AN: 24014

East Asian (EAS) AF: 0.942 AC: 32614 AN: 34638

South Asian (SAS) AF: 0.809 AC: 62108 AN: 76780

European-Finnish (FIN) AF: 0.638 AC: 31961 AN: 50098

Middle Eastern (MID) AF: 0.685 AC: 3754 AN: 5480

European-Non Finnish (NFE) AF: 0.660 AC: 676497 AN: 1024676

Other (OTH) AF: 0.703 AC: 39164 AN: 55686

GnomAD4 genome AF: 0.729 AC: 110921 AN: 152242 Hom.: 40983 Cov.: 34 AF XY: 0.732 AC XY: 54518 AN XY: 74432

African (AFR) AF: 0.807 AC: 33545 AN: 41554

American (AMR) AF: 0.779 AC: 11917 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2348 AN: 3472

East Asian (EAS) AF: 0.956 AC: 4955 AN: 5184

South Asian (SAS) AF: 0.828 AC: 3992 AN: 4822

European-Finnish (FIN) AF: 0.655 AC: 6937 AN: 10592

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44858 AN: 67994

Other (OTH) AF: 0.727 AC: 1536 AN: 2114

Alfa AF: 0.582 Hom.: 1526

Bravo AF: 0.742

Asia WGS AF: 0.885 AC: 3074 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.57
PhyloP100		-0.59
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs4846864; hg19: chr1-230778491;