2-85327013-G-T

Variant names:

• chr2-85327013-G-T
• rs373706229
• NM_006464.4:c.719C>A

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.719C>A​(p.Ala240Glu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A240G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TGOLN2 NM_006464.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• 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=0.06473631).

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.719C>A	p.Ala240Glu	missense	Exon 2 of 4	NP_006455.2
	TGOLN2	NM_001368095.1		c.719C>A	p.Ala240Glu	missense	Exon 2 of 4	NP_001355024.1	O43493-7
	TGOLN2	NM_001368096.1		c.719C>A	p.Ala240Glu	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.719C>A	p.Ala240Glu	missense	Exon 2 of 4	ENSP00000366603.3	O43493-2
	TGOLN2	ENST00000409015.5	TSL:1	c.719C>A	p.Ala240Glu	missense	Exon 2 of 4	ENSP00000387035.1	O43493-7
	TGOLN2	ENST00000409232.7	TSL:1	c.719C>A	p.Ala240Glu	missense	Exon 2 of 4	ENSP00000386443.3	A0A5F9UY30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.9
DANN	Benign	0.64
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.4
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.065
Sift	Benign	0.032	D
Sift4G	Benign	1.0	T
Polyphen		0.77	P
Vest4		0.12
MutPred		0.23		Loss of glycosylation at S238 (P = 0.1175)
MVP		0.061
ClinPred		0.15	T
GERP RS		-6.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.054
gMVP		0.034
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs373706229; hg19: chr2-85554136;