1-230642648-G-T

Variant names:

• chr1-230642648-G-T
• rs369420107
• NM_007357.3:c.42G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007357.3(COG2):​c.42G>T​(p.Thr14Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T14T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COG2 NM_007357.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 0 publications found

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]

COG2 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation, type IIq

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000305699 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=0.031 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007357.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG2	NM_007357.3	MANE Select	c.42G>T	p.Thr14Thr	synonymous	Exon 1 of 18	NP_031383.1	Q14746-1
	COG2	NM_001145036.2		c.42G>T	p.Thr14Thr	synonymous	Exon 1 of 18	NP_001138508.1	Q14746-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG2	ENST00000366669.9	TSL:1 MANE Select	c.42G>T	p.Thr14Thr	synonymous	Exon 1 of 18	ENSP00000355629.4	Q14746-1
	COG2	ENST00000366668.7	TSL:1	c.42G>T	p.Thr14Thr	synonymous	Exon 1 of 18	ENSP00000355628.3	Q14746-2
	COG2	ENST00000921491.1		c.42G>T	p.Thr14Thr	synonymous	Exon 1 of 18	ENSP00000591550.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460780 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726622

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 85936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111624

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.031
PromoterAI		-0.0057	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs369420107; hg19: chr1-230778394;