1-230691841-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.2115+277A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0304 in 346,408 control chromosomes in the GnomAD database, including 228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (70 hom., cov: 32)
  • Exomes 𝑓: 0.035 (158 hom.)
• Consequence: COG2 NM_007357.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.950

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]

AGT (HGNC:333): (angiotensinogen) The protein encoded by this gene, pre-angiotensinogen or angiotensinogen precursor, is expressed in the liver and is cleaved by the enzyme renin in response to lowered blood pressure. The resulting product, angiotensin I, is then cleaved by angiotensin converting enzyme (ACE) to generate the physiologically active enzyme angiotensin II. The protein is involved in maintaining blood pressure, body fluid and electrolyte homeostasis, and in the pathogenesis of essential hypertension and preeclampsia. Mutations in this gene are associated with susceptibility to essential hypertension, and can cause renal tubular dysgenesis, a severe disorder of renal tubular development. Defects in this gene have also been associated with non-familial structural atrial fibrillation, and inflammatory bowel disease. [provided by RefSeq, Nov 2019]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-230691841-A-G is Benign according to our data. Variant chr1-230691841-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1318104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG2	NM_007357.3	c.2115+277A>G		intron_variant		ENST00000366669.9
COG2	NM_001145036.2	c.2112+277A>G		intron_variant
COG2	XM_047449445.1	c.1776+277A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG2	ENST00000366669.9	c.2115+277A>G		intron_variant		1	NM_007357.3	P4

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3744 AN: 152078 Hom.: 70 Cov.: 32

Gnomad AFR AF: 0.00683

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.0301

GnomAD4 exome AF: 0.0350 AC: 6804 AN: 194212 Hom.: 158 Cov.: 0 AF XY: 0.0368 AC XY: 3662 AN XY: 99632

Gnomad4 AFR exome AF: 0.00515

Gnomad4 AMR exome AF: 0.0235

Gnomad4 ASJ exome AF: 0.0528

Gnomad4 EAS exome AF: 0.000212

Gnomad4 SAS exome AF: 0.0785

Gnomad4 FIN exome AF: 0.0275

Gnomad4 NFE exome AF: 0.0362

Gnomad4 OTH exome AF: 0.0367

GnomAD4 genome AF: 0.0246 AC: 3743 AN: 152196 Hom.: 70 Cov.: 32 AF XY: 0.0244 AC XY: 1812 AN XY: 74402

Gnomad4 AFR AF: 0.00681

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.0713

Gnomad4 FIN AF: 0.0207

Gnomad4 NFE AF: 0.0337

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0287 Hom.: 8

Bravo AF: 0.0230

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 06, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.36
Dann	Benign	0.35

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: rs41271497; hg19: chr1-230827587;