1-230677568-A-T

Variant names:

• chr1-230677568-A-T
• rs10495298
• NM_007357.3:c.1027-1345A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007357.3(COG2):​c.1027-1345A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,274 control chromosomes in the GnomAD database, including 1,500 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1500 hom., cov: 32)
• Consequence: COG2 NM_007357.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.186 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG2	NM_007357.3	MANE Select	c.1027-1345A>T		intron	N/A	NP_031383.1
	COG2	NM_001145036.2		c.1027-1345A>T		intron	N/A	NP_001138508.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG2	ENST00000366669.9	TSL:1 MANE Select	c.1027-1345A>T		intron	N/A	ENSP00000355629.4
	COG2	ENST00000366668.7	TSL:1	c.1027-1345A>T		intron	N/A	ENSP00000355628.3
	COG2	ENST00000534989.1	TSL:2	c.850-1345A>T		intron	N/A	ENSP00000440349.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18072 AN: 152156 Hom.: 1501 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.126

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18074 AN: 152274 Hom.: 1500 Cov.: 32 AF XY: 0.124 AC XY: 9242 AN XY: 74458

African (AFR) AF: 0.0275 AC: 1143 AN: 41588

American (AMR) AF: 0.192 AC: 2932 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3468

East Asian (EAS) AF: 0.142 AC: 735 AN: 5184

South Asian (SAS) AF: 0.125 AC: 601 AN: 4822

European-Finnish (FIN) AF: 0.243 AC: 2577 AN: 10600

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.132 AC: 8989 AN: 68020

Other (OTH) AF: 0.125 AC: 263 AN: 2110

Alfa AF: 0.136 Hom.: 232

Bravo AF: 0.113

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.56
DANN	Benign	0.67
PhyloP100		-0.41
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: rs10495298; hg19: chr1-230813314;