1-230691510-C-T
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_007357.3(COG2):c.2061C>T(p.Asp687Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
COG2
NM_007357.3 synonymous
NM_007357.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.159
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 1-230691510-C-T is Benign according to our data. Variant chr1-230691510-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 715155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.159 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000236 (36/152232) while in subpopulation SAS AF= 0.000415 (2/4822). AF 95% confidence interval is 0.000159. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| COG2 | NM_007357.3 | c.2061C>T | p.Asp687Asp | synonymous_variant | 17/18 | ENST00000366669.9 | NP_031383.1 | |
| COG2 | NM_001145036.2 | c.2058C>T | p.Asp686Asp | synonymous_variant | 17/18 | NP_001138508.1 | ||
| COG2 | XM_047449445.1 | c.1722C>T | p.Asp574Asp | synonymous_variant | 15/16 | XP_047305401.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.000237 AC: 36AN: 152114Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000255 AC: 64AN: 251172Hom.: 0 AF XY: 0.000302 AC XY: 41AN XY: 135800
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GnomAD4 exome AF: 0.000168 AC: 246AN: 1461874Hom.: 0 Cov.: 30 AF XY: 0.000184 AC XY: 134AN XY: 727232
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GnomAD4 genome 0.000236 AC: 36AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74428
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Congenital disorder of glycosylation, type IIq Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 04, 2023 | - - |
not provided Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | COG2: BP4, BP7 - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at