1-230660580-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007357.3(COG2):c.235-178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,170 control chromosomes in the GnomAD database, including 2,662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2662 hom., cov: 33)
• Consequence: COG2 NM_007357.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.22

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 1-230660580-A-G is Benign according to our data. Variant chr1-230660580-A-G is described in ClinVar as [Benign]. Clinvar id is 1227643.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG2	NM_007357.3	c.235-178A>G		intron_variant		ENST00000366669.9
COG2	NM_001145036.2	c.235-178A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG2	ENST00000366669.9	c.235-178A>G		intron_variant		1	NM_007357.3	P4

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24884 AN: 152052 Hom.: 2663 Cov.: 33

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.164 AC: 24886 AN: 152170 Hom.: 2662 Cov.: 33 AF XY: 0.167 AC XY: 12458 AN XY: 74382

Gnomad4 AFR AF: 0.0403

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.149

Alfa AF: 0.180 Hom.: 389

Bravo AF: 0.154

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

Sep 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.0020
Dann	Benign	0.58

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: rs3736983; hg19: chr1-230796326;