1-230642745-G-C

Position:

• chr1-230642745-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000366669.9(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 ENST00000366669.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.595

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG2	NM_007357.3	c.72+67G>C		intron_variant		ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2	c.72+67G>C		intron_variant			NP_001138508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9	c.72+67G>C		intron_variant		1	NM_007357.3	ENSP00000355629	P4

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

Gnomad4 AFR exome AF: 0.812

Gnomad4 AMR exome AF: 0.840

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.942

Gnomad4 SAS exome AF: 0.809

Gnomad4 FIN exome AF: 0.638

Gnomad4 NFE exome AF: 0.660

Gnomad4 OTH exome AF: 0.703

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

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.727

Alfa AF: 0.582 Hom.: 1526

Bravo AF: 0.742

Asia WGS AF: 0.885 AC: 3074 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.57

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: rs4846864; hg19: chr1-230778491;