1-230642497-AC-A

Position:

• chr1-230642497-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007357.3(COG2):​c.-104del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 979,088 control chromosomes in the GnomAD database, including 27,242 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4681 hom., cov: 26)
  • Exomes 𝑓: 0.22 (22561 hom.)
• Consequence: COG2 NM_007357.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.936

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-230642497-AC-A is Benign according to our data. Variant chr1-230642497-AC-A is described in ClinVar as [Benign]. Clinvar id is 1232503.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG2	NM_007357.3	c.-104del		5_prime_UTR_variant	1/18	ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2	c.-104del		5_prime_UTR_variant	1/18		NP_001138508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9	c.-104del		5_prime_UTR_variant	1/18	1	NM_007357.3	ENSP00000355629	P4
COG2	ENST00000494371.5	n.15del		non_coding_transcript_exon_variant	1/10	2
COG2	ENST00000468893.6			upstream_gene_variant		2		ENSP00000476305
COG2	ENST00000473671.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36623 AN: 151794 Hom.: 4674 Cov.: 26

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.220 AC: 182076 AN: 827178 Hom.: 22561 Cov.: 6 AF XY: 0.227 AC XY: 94940 AN XY: 417488

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.396

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.241 AC: 36655 AN: 151910 Hom.: 4681 Cov.: 26 AF XY: 0.243 AC XY: 18071 AN XY: 74266

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.240

Alfa AF: 0.0606 Hom.: 70

Bravo AF: 0.246

Asia WGS AF: 0.337 AC: 1172 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 27, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs11361885; hg19: chr1-230778243;