2-85322694-A-G

Position:

• chr2-85322694-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006464.4(TGOLN2):​c.*42T>C variant causes a 3 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TGOLN2 NM_006464.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.347

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1725932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGOLN2	NM_006464.4	c.*42T>C		3_prime_UTR_variant	4/4	ENST00000377386.8	NP_006455.2
TGOLN2	NM_001206844.2	c.*42T>C		3_prime_UTR_variant	5/5		NP_001193773.1
TGOLN2	NM_001368095.1	c.*49T>C		3_prime_UTR_variant	4/4		NP_001355024.1
TGOLN2	NM_001368096.1	c.*11T>C		3_prime_UTR_variant	4/4		NP_001355025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGOLN2	ENST00000377386.8	c.*42T>C		3_prime_UTR_variant	4/4	1	NM_006464.4	ENSP00000366603	A2
TGOLN2	ENST00000398263.6	c.*42T>C		3_prime_UTR_variant	5/5	1		ENSP00000381312	A2
TGOLN2	ENST00000409015.5	c.*49T>C		3_prime_UTR_variant	4/4	1		ENSP00000387035	P5
TGOLN2	ENST00000409232.7	c.*11T>C		3_prime_UTR_variant	4/4	1		ENSP00000386443	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2023

The c.1414T>C (p.W472R) alteration is located in exon 4 (coding exon 4) of the TGOLN2 gene. This alteration results from a T to C substitution at nucleotide position 1414, causing the tryptophan (W) at amino acid position 472 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	10
DANN	Benign	0.74
FATHMM_MKL	Benign	0.12	N
MetaRNN	Benign	0.17	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.43	T
Sift4G	Pathogenic	0.0	D
Vest4		0.43
MVP		0.16
GERP RS		0.52
Varity_R		0.096

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-85549817;