1-230693233-T-C

Position:

• chr1-230693233-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007357.3(COG2):​c.2116-59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 969,500 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (14 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (4 hom.)
• Consequence: COG2 NM_007357.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0150

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=-0.91).
• BP6: Variant 1-230693233-T-C is Benign according to our data. Variant chr1-230693233-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1707266.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00827 (1250/151142) while in subpopulation AFR AF= 0.0251 (1023/40706). AF 95% confidence interval is 0.0239. There are 14 homozygotes in gnomad4. There are 631 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG2	NM_007357.3	c.2116-59T>C		intron_variant		ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2	c.2113-59T>C		intron_variant			NP_001138508.1
COG2	XM_047449445.1	c.1777-59T>C		intron_variant			XP_047305401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9	c.2116-59T>C		intron_variant		1	NM_007357.3	ENSP00000355629	P4

Frequencies

GnomAD3 genomes AF: 0.00822 AC: 1242 AN: 151026 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00784

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00562

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0125

GnomAD4 exome AF: 0.00129 AC: 1057 AN: 818358 Hom.: 4 AF XY: 0.00120 AC XY: 514 AN XY: 429120

Gnomad4 AFR exome AF: 0.0226

Gnomad4 AMR exome AF: 0.00348

Gnomad4 ASJ exome AF: 0.00152

Gnomad4 EAS exome AF: 0.00285

Gnomad4 SAS exome AF: 0.000506

Gnomad4 FIN exome AF: 0.000116

Gnomad4 NFE exome AF: 0.000372

Gnomad4 OTH exome AF: 0.00291

GnomAD4 genome AF: 0.00827 AC: 1250 AN: 151142 Hom.: 14 Cov.: 33 AF XY: 0.00854 AC XY: 631 AN XY: 73914

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.00783

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00583

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.0000945

Gnomad4 NFE AF: 0.000530

Gnomad4 OTH AF: 0.0124

Alfa AF: 0.000693 Hom.: 0

Bravo AF: 0.00918

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

Mar 06, 2020

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.42

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: rs187524214; hg19: chr1-230828979; COSMIC: COSV64188401; COSMIC: COSV64188401;