1-230659431-T-C

Position:

• chr1-230659431-T-C

Variant summary

Our verdict is Benign. Variant got -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, single submitter B:1
• Conservation: PhyloP100: -0.642

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 1-230659431-T-C is Benign according to our data. Variant chr1-230659431-T-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG2	NM_007357.3	c.73-33T>C		intron_variant		ENST00000366669.9
COG2	NM_001145036.2	c.73-33T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG2	ENST00000366669.9	c.73-33T>C		intron_variant		1	NM_007357.3	P4

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

GnomAD3 exomes AF: 0.680 AC: 169067 AN: 248680 Hom.: 58770 AF XY: 0.675 AC XY: 90996 AN XY: 134814

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 SAS exome AF: 0.761

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

Gnomad4 AFR exome AF: 0.757

Gnomad4 AMR exome AF: 0.767

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.854

Gnomad4 SAS exome AF: 0.758

Gnomad4 FIN exome AF: 0.618

Gnomad4 NFE exome AF: 0.603

Gnomad4 OTH exome AF: 0.645

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

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.660

Alfa AF: 0.620 Hom.: 30822

Bravo AF: 0.680

Asia WGS AF: 0.820 AC: 2849 AN: 3478

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 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.27

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: rs1359866; hg19: chr1-230795177;