2-85326661-C-A

Variant names:

• chr2-85326661-C-A
• rs1044973
• NM_006464.4:c.1071G>T

Variant summary

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

The NM_006464.4(TGOLN2):​c.1071G>T​(p.Gly357Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TGOLN2 NM_006464.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 37 publications found

Genes affected

TGOLN2 (HGNC:15450): (trans-golgi network protein 2) This gene encodes a type I integral membrane protein that is localized to the trans-Golgi network, a major sorting station for secretory and membrane proteins. The encoded protein cycles between early endosomes and the trans-Golgi network, and may play a role in exocytic vesicle formation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

ENSG00000307411 (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=-0.67).
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006464.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGOLN2	NM_006464.4	MANE Select	c.1071G>T	p.Gly357Gly	synonymous	Exon 2 of 4	NP_006455.2
	TGOLN2	NM_001368095.1		c.1071G>T	p.Gly357Gly	synonymous	Exon 2 of 4	NP_001355024.1
	TGOLN2	NM_001368096.1		c.1071G>T	p.Gly357Gly	synonymous	Exon 2 of 4	NP_001355025.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGOLN2	ENST00000377386.8	TSL:1 MANE Select	c.1071G>T	p.Gly357Gly	synonymous	Exon 2 of 4	ENSP00000366603.3
	TGOLN2	ENST00000409015.5	TSL:1	c.1071G>T	p.Gly357Gly	synonymous	Exon 2 of 4	ENSP00000387035.1
	TGOLN2	ENST00000409232.7	TSL:1	c.1071G>T	p.Gly357Gly	synonymous	Exon 2 of 4	ENSP00000386443.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 88

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.3
DANN	Benign	0.75
PhyloP100		-1.1
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1044973; hg19: chr2-85553784;