1-230659431-T-C

Variant names:

• chr1-230659431-T-C
• rs1359866
• NM_007357.3:c.73-33T>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.73-33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 1,561,318 control chromosomes in the GnomAD database, including 318,743 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34698 hom., cov: 32)
  • Exomes 𝑓: 0.63 (284045 hom.)
• Consequence: COG2 NM_007357.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.642
• Publications: 7 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 1-230659431-T-C is Benign according to our data. Variant chr1-230659431-T-C is described in ClinVar as Benign. ClinVar VariationId is 1285989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 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.73-33T>C		intron	N/A	NP_031383.1	Q14746-1
	COG2	NM_001145036.2		c.73-33T>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.73-33T>C		intron	N/A	ENSP00000355629.4	Q14746-1
	COG2	ENST00000366668.7	TSL:1	c.73-33T>C		intron	N/A	ENSP00000355628.3	Q14746-2
	COG2	ENST00000921491.1		c.73-33T>C		intron	N/A	ENSP00000591550.1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101856 AN: 151906 Hom.: 34649 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.656

GnomAD2 exomes AF: 0.680 AC: 169067 AN: 248680 AF XY: 0.675

Gnomad AFR exome AF: 0.756

Gnomad AMR exome AF: 0.773

Gnomad ASJ exome AF: 0.612

Gnomad EAS exome AF: 0.922

Gnomad FIN exome AF: 0.625

Gnomad NFE exome AF: 0.598

Gnomad OTH exome AF: 0.649

GnomAD4 exome AF: 0.631 AC: 888944 AN: 1409294 Hom.: 284045 Cov.: 23 AF XY: 0.633 AC XY: 446072 AN XY: 704252

African (AFR) AF: 0.757 AC: 24480 AN: 32328

American (AMR) AF: 0.767 AC: 34123 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 15775 AN: 25798

East Asian (EAS) AF: 0.854 AC: 33715 AN: 39480

South Asian (SAS) AF: 0.758 AC: 64403 AN: 84952

European-Finnish (FIN) AF: 0.618 AC: 32737 AN: 52964

Middle Eastern (MID) AF: 0.590 AC: 3337 AN: 5656

European-Non Finnish (NFE) AF: 0.603 AC: 642503 AN: 1064940

Other (OTH) AF: 0.645 AC: 37871 AN: 58698

GnomAD4 genome AF: 0.671 AC: 101966 AN: 152024 Hom.: 34698 Cov.: 32 AF XY: 0.675 AC XY: 50160 AN XY: 74288

African (AFR) AF: 0.747 AC: 30947 AN: 41442

American (AMR) AF: 0.702 AC: 10724 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2112 AN: 3472

East Asian (EAS) AF: 0.901 AC: 4665 AN: 5176

South Asian (SAS) AF: 0.764 AC: 3676 AN: 4814

European-Finnish (FIN) AF: 0.634 AC: 6707 AN: 10572

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40958 AN: 67976

Other (OTH) AF: 0.660 AC: 1384 AN: 2098

Alfa AF: 0.627 Hom.: 40383

Bravo AF: 0.680

Asia WGS AF: 0.820 AC: 2849 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	0.39
DANN	Benign	0.27
PhyloP100		-0.64
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: rs1359866; hg19: chr1-230795177;