2-85327016-C-A

Variant names:

• chr2-85327016-C-A
• NM_006464.4:c.716G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006464.4(TGOLN2):​c.716G>T​(p.Gly239Val) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TGOLN2 NM_006464.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.74
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033337444).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGOLN2	NM_006464.4	MANE Select	c.716G>T	p.Gly239Val	missense	Exon 2 of 4	NP_006455.2
	TGOLN2	NM_001368095.1		c.716G>T	p.Gly239Val	missense	Exon 2 of 4	NP_001355024.1	O43493-7
	TGOLN2	NM_001368096.1		c.716G>T	p.Gly239Val	missense	Exon 2 of 4	NP_001355025.1	A0A5F9UY30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGOLN2	ENST00000377386.8	TSL:1 MANE Select	c.716G>T	p.Gly239Val	missense	Exon 2 of 4	ENSP00000366603.3	O43493-2
	TGOLN2	ENST00000409015.5	TSL:1	c.716G>T	p.Gly239Val	missense	Exon 2 of 4	ENSP00000387035.1	O43493-7
	TGOLN2	ENST00000409232.7	TSL:1	c.716G>T	p.Gly239Val	missense	Exon 2 of 4	ENSP00000386443.3	A0A5F9UY30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.77
DANN	Benign	0.37
DEOGEN2	Benign	0.016	T
Eigen	Benign	-2.5
Eigen_PC	Benign	-2.7
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.0	L
PhyloP100		-3.7
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.052
Sift	Benign	0.14	T
Sift4G	Benign	0.082	T
Polyphen		0.83	P
Vest4		0.074
MutPred		0.22		Loss of glycosylation at S238 (P = 0.0358)
MVP		0.088
ClinPred		0.18	T
GERP RS		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.046
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chr2-85554139;